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1.
BMC Complement Altern Med ; 19(1): 246, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488172

RESUMO

BACKGROUND: Yangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesity in high-fat diet (HFD)-induced obese mice. METHODS: We induced obesity in C57bl/6 J mice using a HFD, and then orally administered 300 mg/kg YST for 6 weeks. We measured body weight, food efficiency, organ and fat weight, serum biochemical parameters, and obesity-related gene expression, and carried out histological analysis at the end of the experimental period. RESULTS: YST significantly reduced the absolute body weight and food efficiency ratio. The serum, aminotransferase, glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels were significantly lower in the YST-treated group than in the control group, whereas the high-density lipoprotein-cholesterol level in the YST-treated group was significantly higher. The YST-treated group also showed a significant reduction in regional fatty tissues and the absolute weight of various organs. We also observed a significantly reduced expression of AP2/FABP4, C/EBP-ß, leptin, and SREBP1c/ADD1 mRNA, and significantly increased expression of UCP-2 and adiponectin mRNA in adipose tissue in the YST-treated group. YST also decreased the lipid droplet size and lipid accumulation in the liver, as well as adipocyte size in epididymal adipose tissue. At the dose tested, YST was non-toxic to the liver and kidneys of the mice. CONCLUSION: The results imply that YST has anti-obesity effects in obesity-induced mice. Although the number of experimental animals was limited and the drug effects concern mice, rather than humans, which have different constitutions, the study has valuable implications with respect to the general effects of YST.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Fármacos Antiobesidade/química , Peso Corporal/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , HDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Leptina/genética , Leptina/metabolismo , Masculino , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Extratos Vegetais/química , Plantas Medicinais/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
2.
Cancer Biother Radiopharm ; 34(8): 537-546, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31314588

RESUMO

Introduction: Growth differentiation factor 15 (GDF15), a newly identified member of transforming growth factor (GDF) superfamily, is upregulated in ovarian (OV) cancer. Upregulated GDF15 positively correlates with poor prognosis of OV cancer. Thus, elucidation of the mechanism underlying GDF15 overexpression is important. Method and Results: PROMO and JASPAR prediction software were used to find transcription factors for GDF15 expression. Data from TCGA database were analyzed to find long noncoding RNAs (lncRNAs) that were also abnormally expressed in OV cancer and had associations with GDF15 expression. Transcription factor CEBPB was predicted as an important regulator of GDF15, confirmed by luciferase reporter assay. However, CEBPB expression was not significantly changed in OV cancer. Data from TCGA database showed that lncRNA GAS5 is downregulated in OV cancer and its expression is negatively correlated with GDF15 expression. RPISeq showed high affinity of GAS5 to CEBPB and this was confirmed by RNA-binding protein immunoprecipitation assay. GAS5 overexpression increased its binding to CEBPB and consequently downregulated GDF15. GAS5 overexpression and GDF15 knockdown decreased viability and increased apoptosis of OV cancer cells, but CEBPB overexpression had opposite effects. However, simultaneous GAS5 and CEBPB overexpression or CEBPB overexpression together with GDF15 knockdown had no effect on cell viability and apoptosis. Conclusion: GAS5 functions as decoy of CEBPB, blocking transcription-promoting effect of CEBPB on GDF15.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Fator 15 de Diferenciação de Crescimento/metabolismo , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , Estudos de Casos e Controles , Feminino , Fator 15 de Diferenciação de Crescimento/genética , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , RNA Longo não Codificante/genética , Células Tumorais Cultivadas
3.
Biochim Biophys Acta Gene Regul Mech ; 1862(9): 194412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31356989

RESUMO

Non-alcoholic steatohepatitis (NASH) is one of the most predominant disorders in metabolic syndrome. Induction of pro-inflammatory mediators in hepatocytes exposed to free fatty acids represents a hallmark event during NASH pathogenesis. C-reactive protein (CRP) is a prototypical pro-inflammatory mediator. In the present study, we investigated the mechanism by which megakaryocytic leukemia 1 (MKL1) mediates palmitate (PA) induced CRP transcription in hepatocytes. We report that over-expression of MKL1, but not MKL2, activated the CRP promoter whereas depletion or inhibition of MKL1 repressed the CRP promoter. MKL1 potentiated the induction of the CRP promoter activity by PA treatment. Importantly, MKL1 knockdown by siRNA or pharmaceutical inhibition by CCG-1423 attenuated the induction of endogenous CRP expression in hepatocytes. Similarly, primary hepatocytes isolated from wild type (WT) mice produced more CRP than those isolated from MKL1 deficient (KO) mice when stimulated with PA. Mechanistically, the sequence-specific transcription factor CCAAT-enhancer-binding protein (C/EBPß) interacted with MKL1 and recruited MKL1 to activate CRP transcription. Reciprocally, MKL1 modulated C/EBPß activity by recruiting the chromatin remodeling protein BRG1 to the CRP promoter to alter histone modifications. In conclusion, our data delineate a novel epigenetic mechanism underlying augmented hepatic inflammation during NASH pathogenesis.


Assuntos
Proteína C-Reativa/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , DNA Helicases/genética , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas Nucleares/genética , Transativadores/genética , Fatores de Transcrição/genética , Animais , Proteína C-Reativa/química , Proteína beta Intensificadora de Ligação a CCAAT/química , Montagem e Desmontagem da Cromatina/genética , Regulação da Expressão Gênica/genética , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/patologia , Regiões Promotoras Genéticas , Transativadores/química
4.
Neoplasia ; 21(6): 545-556, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31042624

RESUMO

CD133 is a cellular surface protein, which has been reported to be a cancer stem cell marker, and thus is considered a potential target for cancer treatment. Metformin, one of the biguanides used for the treatment of diabetes, is also known to reduce the risk of cancer development and cancer stem-like cells (CSCs), including the expression of CD133. However, the mechanism underlying the reduction of the expression of CD133 by metformin is not yet understood. This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR). AMPK inhibition rescued the reduction of CD133 by metformin. Further experiments demonstrated that CCAAT/enhancer-binding protein beta (CEBPß) was upregulated by metformin and that two isoforms of CEBPß reciprocally regulated the expression of CD133. Specifically, the liver-enriched activator protein (LAP) isoform increased the expression of CD133 by directly binding to the P1 promoter region, whereas the liver-enriched inhibitory protein (LIP) isoform suppressed the expression of CD133. Consistent with these findings, a three dimensional (3D) culture assay and drug sensitivity assay demonstrated that LAP-overexpressing cells formed large spheroids and were more resistant to 5-fluorouracil (5-FU) treatment, whereas LIP-overexpressing cells were more sensitive to 5-FU and showed combined effects with metformin. Our results indicated that metformin-AMPK-CEBPß signaling plays a crucial role in regulating the gene expression of CD133. Additionally, regulating the ratio of LAP/LIP may be a novel strategy for targeting CSCs for the treatment of cancer.


Assuntos
Antígeno AC133/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Quinases/genética , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metformina/farmacologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Toxicol Lett ; 312: 11-21, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31059759

RESUMO

Methamphetamine (METH) is a widely abused illicit psychoactive drug. Our previous study has shown that CCAAT-enhancer binding protein ß (C/EBPß) is an important regulator in METH-induced neuronal autophagy and apoptosis. However, the detailed molecular mechanisms underlying this process remain poorly understood. Previous studies have demonstrated that DNA damage-inducible transcript 4 (DDIT4), Trib3 (tribbles pseudo kinase 3), alpha-synuclein (α-syn) are involved in METH-induced dopaminergic neurotoxicity. We hypothesized that C/EBPß is involved in METH-induced DDIT4-mediated neuronal autophagy and Trib3-mediated neuronal apoptosis. We tested our hypothesis by examining the effects of silencing C/EBPß, DDIT4, Trib3 or α-syn with small interfering ribonucleic acid (siRNA) on METH-induced autophagy and apoptosis in the human neuroblastoma SH-SY5Y cells. We also measured the levels of phosphorylated tuberous sclerosis complex 2 (TSC2) protein and Parkin protein level in SH-SY5Y cells. Furthermore, we demonstrated the effect of silencing C/EBPß on METH-caused neurotoxicity in the striatum of rats by injecting LV-shC/EBPß lentivirus using a stereotaxic positioning system. The results showed that METH exposure increased C/EBPß, DDIT4 protein expression. Elevated DDIT4 expression raised up p-TSC2/TSC2 protein expression ratio, inhibited mTOR signaling pathway, activating cell autophagy. We also found that METH exposure increased the expression of Trib3, α-syn, decreased the Parkin protein expression. Lowering levels of Parkin raised up α-syn expression, which initiated mitochondrial apoptosis by down-regulating anti-apoptotic Bcl-2, followed by up-regulation of pro-apoptotic Bax, resulting in translocation of cytochrome c (cyto c), an apoptogenic factor, from the mitochondria to cytoplasm and activation of caspase-dependent pathways. These findings were supported by data showing METH-induced autophagy and apoptosis was significantly inhibited by silencing C/EBPß, DDIT4, Trib3 or α-syn, or by Parkin over-expression. Based on the present data, a novel of mechanism on METH-induced cell toxicity is proposed, METH exposure increased C/EBPß protein expression, triggered DDIT4/TSC2/mTOR signaling pathway, and evoked Trib3/Parkin/α-syn-related mitochondrial apoptotic signaling pathway. Collectively, these results suggest that C/EBPß plays an important role in METH-triggered autophagy and apoptosis and it may be a potential target for therapeutics in METH-caused neurotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Estimulantes do Sistema Nervoso Central/toxicidade , Metanfetamina/toxicidade , Neurônios/efeitos dos fármacos , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Masculino , Neuroblastoma , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
6.
Mol Immunol ; 112: 72-81, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31078118

RESUMO

Myeloid-derived suppressor cells (MDSC) expand during sepsis, suppress both innate and adaptive immunity, and promote chronic immunosuppression, which characterizes the late/chronic phase of sepsis. We previously reported that the transcription factors Stat3 and C/EBPß synergize to induces the expression of microRNA (miR)-21 and miR-181b to promote MDSC expansion in a mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive stage. We also showed that Gr1+CD11b+ cells, the precursors of MDSCs, from mice genetically deficient in the inflammatory protein S100A9 lack miR-21 or miR-181b in late sepsis, and are not immunosuppressive. In the present study, we show that S100A9 induces miR-21 and miR-181b during the late sepsis phase. We find that S100A9 associates with and stabilizes the Stat3-C/EBPß protein complex that activates the miRNA promoters. Reconstituting Gr1+CD11b+ cells from S100A9 knockout mice with late sepsis with S100A9 protein restores the Stat3-C/EBPß protein complex and miRNA expressions, and switches the Gr1+CD11b+ cells into the immunosuppressive, MDSC phenotype. Importantly, we find that this process requires IL-10 mediated signaling, which induces S100A9 translocation from the cytosol to the nucleus. These results demonstrate that S100A9 promotes MDSC expansion and immunosuppression in late/chronic sepsis by inducing the expression of miR-21 and miR-181b.


Assuntos
Calgranulina B/genética , MicroRNAs/genética , Células Mieloides/metabolismo , Células Supressoras Mieloides/metabolismo , Sepse/genética , Animais , Antígenos Ly/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , Antígeno CD11b/genética , Modelos Animais de Doenças , Imunossupressão/métodos , Inflamação/genética , Interleucina-10/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética
7.
J Biol Chem ; 294(24): 9642-9654, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31061100

RESUMO

ß-Catenin signaling is triggered by WNT proteins and is an important pathway that negatively regulates adipogenesis. However, the mechanisms controlling the expression of WNT proteins during adipogenesis remain incompletely understood. Lysine demethylase 5A (KDM5A) is a histone demethylase that removes trimethyl (me3) marks from lysine 4 of histone 3 (H3K4) and serves as a general transcriptional corepressor. Here, using the murine 3T3-L1 preadipocyte differentiation model and an array of biochemical approaches, including ChIP, immunoprecipitation, RT-qPCR, and immunoblotting assays, we show that Kdm5a is a target gene of CCAAT/enhancer-binding protein ß (C/EBPß), an important early transcription factor required for adipogenesis. We found that C/EBPß binds to the Kdm5a gene promoter and transactivates its expression. We also found that siRNA-mediated KDM5A down-regulation inhibits 3T3-L1 preadipocyte differentiation. The KDM5A knockdown significantly up-regulates the negative regulator of adipogenesis Wnt6, having increased levels of the H3K4me3 mark on its promoter. We further observed that WNT6 knockdown significantly rescues adipogenesis inhibited by the KDM5A knockdown. Moreover, we noted that C/EBPß negatively regulates Wnt6 expression by binding to the Wnt6 gene promoter and repressing Wnt6 transcription. Further experiments indicated that KDM5A interacts with C/EBPß and that their interaction cooperatively inhibits Wnt6 transcription. Of note, C/EBPß knockdown impaired the recruitment of KDM5A to the Wnt6 promoter, which had higher H3K4me3 levels. Our results suggest a mechanism involving C/EBPß and KDM5A activities that down-regulates the Wnt/ß-catenin pathway during 3T3-L1 preadipocyte differentiation.


Assuntos
Adipócitos/citologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Ativação Transcricional , Proteína Wnt1/metabolismo , beta Catenina/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Adipogenia , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Regulação da Expressão Gênica , Histonas/genética , Histonas/metabolismo , Camundongos , Regiões Promotoras Genéticas , Proteína 2 de Ligação ao Retinoblastoma/genética , Proteína Wnt1/genética , beta Catenina/genética
8.
Br Poult Sci ; 60(4): 347-356, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31064204

RESUMO

1. CCAAT/enhancer binding proteins (C/EBPs), as a family of transcription factors, consists of six functionally and structurally related proteins which share a conserved basic leucine zipper (bZIP) DNA-binding domain. The aim of this study was to clone the full-length coding sequences (CDS) of C/EBP-α and -ß genes, and determine the abundance of these two genes in various tissues of white king pigeon (C. livia). 2. The complete cDNA sequences of C/EBP-α and -ß genes were cloned from pigeons by using PCR combined with rapid amplification of cDNA ends (RACE). The sequences were bioinformatically analysed, and the tissue distribution determined by quantitative real-time RT-PCR (qRT-PCR). 3. The results showed that the full-length cDNA sequences of pigeon C/EBP-α and -ß genes were 2,807bp and 1,778bp, respectively. The open reading frames of C/EBP-α (978 bp) and -ß (987bp) encoded 325 amino acids and 328 amino acids, respectively. The pigeon C/EBP-α and C/EBP-ß proteins were predicted to have a conserved basic leucine zipper (bZIP) domain, which is a common structure feature of the C/EBP family. Multiple sequence alignments indicated that pigeon C/EBP-α and -ß shared more than 90% amino-acid identity with their corresponding homologues in other avian species. Phylogenetic analysis revealed that these two proteins were highly conserved across different species and evolutionary processes. QRT-PCR results indicated that the pigeon C/EBP-α and -ß mRNA transcripts were expressed in all investigated organs. The mRNA expression levels of pigeon C/EBP-α in descending order, were in spleen, heart, liver, lung, kidney and muscle. The pigeon C/EBP-ß gene had the most abundant expression in lung, followed by the kidney, with minimal expression detected in muscle. 4. This study investigated the full-length cDNA sequences, genetic characteristics and tissue distribution of pigeon C/EBP-α and -ß genes and found that they may have functions in various tissues of pigeon. This provides a foundation for further study for regulatory mechanisms of these two genes in birds.


Assuntos
Proteínas Aviárias/genética , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , Columbidae/genética , Sequência de Aminoácidos , Animais , Proteínas Aviárias/química , Proteínas Aviárias/metabolismo , Sequência de Bases , Proteína alfa Estimuladora de Ligação a CCAAT/química , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/química , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Clonagem Molecular , Columbidae/metabolismo , Perfilação da Expressão Gênica/veterinária , Filogenia , Alinhamento de Sequência/veterinária
9.
Cancer Sci ; 110(6): 2050-2062, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945396

RESUMO

The PPAR coactivator-1α (PGC1α) is an important transcriptional co-activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1α is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1α could sensitize NPC cells to radiotherapy. Mechanically, PGC1α binds to CCAAT/enhancer binding protein ß (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1α/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1α could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1α might improve the therapeutic efficacy of radiotherapy.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Carnitina O-Palmitoiltransferase/genética , Ácidos Graxos/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Estimativa de Kaplan-Meier , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Oxirredução/efeitos da radiação , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos da radiação , Interferência de RNA
10.
Genet Test Mol Biomarkers ; 23(5): 304-309, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30969151

RESUMO

Aims: Metastasis is a significant obstacle to curing esophageal squamous cell carcinoma (ESCC). The CCAAT/enhancer binding protein ß (C/EBPß) and matrix metalloproteinase 3 (MMP3) are thought to play key roles in cancer invasion and metastasis. In this study, we aimed to detect whether C/EBPß-mediated tumor invasion was dependent on MMP3. In addition, we determined whether C/EBPß upregulation was associated with MMP3 levels and metastatic status in patients with ESCC. Materials and Methods: A total of 126 patients with ESCC were recruited for this study. The mRNA and protein levels of C/EBPß and MMP3 in ESCC cell lines and specimens from ESCC patient were determined by reverse transcription-polymerase chain reaction and western blot, respectively. Tumor cell invasion was analyzed using an in vitro Matrigel Invasion Assay. The correlation between C/EBPß and MMP3 expression was determined by Pearson's correlation analysis. Results: Both mRNA and protein levels of MMP3 were upregulated by C/EBPß overexpression and downregulated by C/EBPß siRNA in KYSE150 cell cultures. The promotion of ESCC cell invasion through C/EBPß was inhibited by MMP3 siRNA. The level of C/EBPß was correlated with MMP3 and metastatic status in patients with ESCC. Conclusions: C/EBPß upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in ESCC.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Carcinoma de Células Escamosas do Esôfago/genética , Metaloproteinase 3 da Matriz/fisiologia , Idoso , Proteína beta Intensificadora de Ligação a CCAAT/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , China , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Regulação para Cima
11.
Am J Physiol Endocrinol Metab ; 316(6): E1081-E1092, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964708

RESUMO

Musclin is a muscle-secreted cytokine that disrupts glucose uptake and glycogen synthesis in type 2 diabetes. The purpose of this study was to investigate the mechanisms responsible for the regulation of musclin gene expression in response to treatment with palmitate. RNA sequencing results showed that biological processes activated by palmitate are mainly enriched in endoplasmic reticulum (ER) stress. The protein kinase RNA-like ER kinase (PERK) signaling pathway is involved in the regulation of musclin expression induced by palmitate. Chromatin immunoprecipitation data showed that activating transcription factor 4 (ATF4)-downstream of PERK-bound to the promoter of the C/EBPß gene. Notably, C/EBPß also contains a binding site in the region -94~-52 of the musclin gene promoter. Knockdown or knockout of PERK and ATF4 using short hairpin RNA or CRISPR-Cas9 decreased the expression of C/EBPß and musclin induced by palmitate. Furthermore, knockdown and knockout of C/EBPß alleviated the high expression of musclin in response to treatment with palmitate. Moreover, CRISPR-Cas9 knockout of the region -94~-52 in which C/EBPß binds to the promoter of musclin abrogated the induction of high musclin expression caused by palmitate. Collectively, these findings suggest that treatment with palmitate activates the PERK/ATF4 signaling pathway, which in turn increases the expression of C/EBPß. C/EBPß binds directly to the promoter of the musclin gene and upregulates its expression.


Assuntos
Fator 4 Ativador da Transcrição/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Proteínas Musculares/efeitos dos fármacos , Palmitatos/farmacologia , Fatores de Transcrição/efeitos dos fármacos , eIF-2 Quinase/efeitos dos fármacos , Fator 4 Ativador da Transcrição/metabolismo , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Regiões Promotoras Genéticas , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , eIF-2 Quinase/metabolismo
12.
Biochim Biophys Acta Gene Regul Mech ; 1862(4): 486-492, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30825655

RESUMO

The bZIP homodimers CEBPB and CREB1 bind DNA containing methylated cytosines differently. CREB1 binds stronger to the C/EBP half-site GCAA when the cytosine is methylated. For CEBPB, methylation of the same cytosine does not affect DNA binding. The X-ray structure of CREB1 binding the half site GTCA identifies an alanine in the DNA binding region interacting with the methyl group of T, structurally analogous to the methyl group of methylated C. This alanine is replaced with a valine in CEBPB. To explore the contribution of this amino acid to binding with methylated cytosine of the GCAA half-site, we made the reciprocal mutants CEBPB(V285A) and CREB1(A297V) and used protein binding microarrays (PBM) to examine binding to four types of double-stranded DNA (dsDNA): 1) DNA with cytosine in both strands (DNA(C|C)), 2) DNA with 5-methylcytosine (M) in one strand and cytosine in the second strand (DNA(M|C)), 3) DNA with 5-hydroxymethylcytosine (H) in one strand and cytosine in the second strand (DNA(H|C)), and 4) DNA with both cytosines in all CG dinucleotides containing 5-methylcytosine (DNA(5mCG)). When binding to DNA(C|C), CEBPB (V285A) preferentially binds the CRE consensus motif (TGACGTCA), similar to CREB1. The reciprocal mutant, CREB1(A297V) binds DNA with some similarity to CEBPB, with strongest binding to the methylated PAR site 8-mer TTACGTAA. These data demonstrate that V285 residue inhibits CEBPB binding to methylated cytosine of the GCAA half-site.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Metilação de DNA , DNA/metabolismo , Sequência de Bases , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Citosina/metabolismo , DNA/química , Mutação , Motivos de Nucleotídeos , Polimorfismo de Nucleotídeo Único , Análise Serial de Proteínas , Ligação Proteica
13.
Biochem Biophys Res Commun ; 511(2): 404-408, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30808546

RESUMO

Claudin-4 (CLDN4), a crucial member of tight junction proteins, is aberrantly expressed in breast cancer cells and contributes to cell migration and invasion. However, the mechanisms controlling CLDN4 expression in breast cancer are poorly understood. Here, we reported that CLDN4 expression correlated positively with p21-activated kinase 4 (PAK4) expression in human breast cancer tissues. Knockdown of PAK4 in MDA-MB-231 and ZR-75-30 cells suppressed CLDN4 expression and significantly inhibited cell migration and invasion. Conversely, restoration of CLDN4 expression in PAK4-knockdown cells reversed the inhibition of migration and invasion. We identified CCAAT/enhancer-binding protein ß (CEBPB) as a novel transcriptional regulator of CLDN4 and confirmed that CEBPB bound to the -1093 to -991 bp region of the CLDN4 promoter. Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr-235. In summary, we showed that PAK4-mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion. Our results might contribute to understanding the mechanisms of CLDN4 regulation and suggest PAK4-CEBPB-CLDN4 axis as a potential therapeutic target for breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Claudina-4/metabolismo , Transdução de Sinais , Quinases Ativadas por p21/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Movimento Celular , Claudina-4/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosforilação , Quinases Ativadas por p21/genética
14.
Mol Med Rep ; 19(3): 2413-2420, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664211

RESUMO

Calprotectin in mucosal epidermal keratinocytes has an important role in fighting microbial infections. S100A8 belongs to the S100 protein family and is a subunit of calprotectin (heterodimer complex of S100A8/A9). Interleukin­1α (IL­1α) is one of the cytokines produced by oral keratinocytes. The primary aims of the present study were to investigate the effect of IL­1α on the expression of S100A8 and its underlying molecular mechanism in oral epithelial cells. Determining the molecular mechanism of the induced expression of S100A8 by IL­1α aims to improve current understanding of the roles of calprotectin during the infection of mucosal epithelial cells. The expression analysis indicated that IL­1α significantly induced the expression of S100A8 in human TR146 epithelial cells at the mRNA and protein levels, respectively. The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL­1α was dependent on the S100A8 promoter specific region (­165/­111). The results of electrophoresis mobility shift assay and chromatin immunoprecipitation assay also demonstrated that the CCAAT/enhancer binding protein ß (C/EBPß) binding site (­113/­109) in the S100A8 promoter region was involved into the upregulatory effect on the expression of S100A8 induced by IL­1α. Taken together, these results suggested that the activation of the expression of S100A8 induced by IL­1α in TR146 epithelial cells involves a mechanism by which the binding activity of C/EBPß to the specific site (­113/­109) of the S100A8 promoter is increased.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Calgranulina A/genética , Células Epiteliais/metabolismo , Interleucina-1alfa/genética , Sítios de Ligação/genética , Epiderme/crescimento & desenvolvimento , Epiderme/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Queratinócitos/metabolismo , Mucosa Bucal/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica/genética
15.
Cell Death Dis ; 10(1): 16, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30622240

RESUMO

Adipogenesis is a process which induces or represses many genes in a way to drive irreversible changes of cell phenotypes; lipid accumulation, round cell-shape, secreting many adipokines. As a master transcription factor (TF), PPARγ2 induces several target genes to orchestrate these adipogenic changes. Thus induction of Pparg2 gene is tightly regulated by many adipogenic and also anti-adipogenic factors. Four hours after the treatment of adipogenic hormones, more than fifteen TFs including glucocorticoid receptor (GR), C/EBPß and AP-1 cooperatively bind the promoter of Pparg2 gene covering 400 bps, termed "hotspot". In this study, we show that TEA domain family transcription factor (TEAD)4 reinforces occupancy of both GR and C/EBPß on the hotspot of Pparg2 during early adipogenesis. Our findings that TEAD4 requires GR for its expression and for the ability to bind its own promoter and the hotspot region of Pparg2 gene indicate that GR is a common component of two positive circuits, which regulates the expression of both Tead4 and Pparg2. Wnt3a disrupts these mutually related positive circuits by limiting the nuclear location of GR in a ß-catenin dependent manner. The antagonistic effects of ß-catenin extend to cytoskeletal remodeling during the early phase of adipogenesis. GR is necessary for the rearrangements of both cytoskeleton and chromatin of Pparg2, whereas Wnt3a inhibits both processes in a ß-catenin-dependent manner. Our results suggest that hotspot formation during early adipogenesis is related to cytoskeletal remodeling, which is regulated by the antagonistic action of GR and ß-catenin, and that Wnt3a reinforces ß-catenin function.


Assuntos
Adipogenia/fisiologia , Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Musculares/metabolismo , PPAR gama/metabolismo , Receptores de Glucocorticoides/metabolismo , Fatores de Transcrição/metabolismo , Proteína Wnt3A/metabolismo , beta Catenina/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Cromatina/metabolismo , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Camundongos , Proteínas Musculares/genética , Células NIH 3T3 , Regiões Promotoras Genéticas , Receptores de Glucocorticoides/genética , Fatores de Transcrição/genética , Transfecção , beta Catenina/genética
16.
Food Chem Toxicol ; 123: 169-180, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30367912

RESUMO

6-n-propyl-2-thiouracil (PTU), a thioamide drug, is used as an effective anti-thyroid agent to treat hyperthyroidism and Graves' disease. However, acute liver oxidative damage is an important side effect of the drug. In the present study, we report that PTU administration to rat induces hepatic epigenetic changes by upregulating expression of DNMT1, DNMT3a, DNMT3b, MBD4, MeCP2, p53 and Gadd45a and down-regulation of PCNA and C/EBP-ß. This is accompanied by decrease in the cell population and augmentation of cellular lipid peroxidation, an index of oxidative stress, in liver. On the other hand, co-administration of curcumin, a polyphenol extract from the rhizome of Curcuma longa L, along with PTU ameliorates PTU- induced oxidative stress and epigenetic parameters except for the expression of MBD4. Also, co-administration of curcumin with PTU resulted in restoration of hepatic cell population and histoarchitecture. The protective effect of curcumin to PTU-induced hepatotoxicity is attributed to its antioxidative properties.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas de Ciclo Celular/metabolismo , Curcumina/administração & dosagem , DNA (Citosina-5-)-Metiltransferases/metabolismo , Endodesoxirribonucleases/metabolismo , Epigênese Genética/efeitos dos fármacos , Hipotireoidismo/tratamento farmacológico , Proteínas Nucleares/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas de Ciclo Celular/genética , Curcuma/química , DNA (Citosina-5-)-Metiltransferases/genética , Endodesoxirribonucleases/genética , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/genética , Hipotireoidismo/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Proteínas Nucleares/genética , Antígeno Nuclear de Célula em Proliferação/genética , Propiltiouracila/efeitos adversos , Ratos
17.
Prostate ; 79(5): 435-445, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30536410

RESUMO

BACKGROUND: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-ß (C/EBPß). METHODS: To explore this further, we examined C/EBPß expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors-and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting. RESULTS: In rats, C/EBPß mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPß was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPß expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBPß in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBPß in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome. CONCLUSIONS: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Processos de Crescimento Celular/fisiologia , Estudos de Coortes , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Receptores ErbB/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Metástase Neoplásica , Transplante de Neoplasias , Fosforilação , Isoformas de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Análise Serial de Tecidos
18.
Ecotoxicol Environ Saf ; 170: 391-398, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550969

RESUMO

BACKGROUND: Plasticizer di-2-ethylhexyl phthalate (DEHP) can induce lipid metabolic disorder. There was a chronic low level inflammatory response in adipose tissue of patients with lipid metabolic disorder. But the effect of inflammation on lipid metabolic disorder induced by DEHP is unclear. The present study was undertaken to explore the effect of di-2-ethylhexyl phthalate on inflammation and lipid metabolic disorder in rats. METHODS: Eighty healthy 21-day-old Wistar rats were randomly divided into 4 groups and administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/ d for 8 weeks. Morphological changes of adipose tissue, the levels of IL-1ß, TNF-α, LEP, and ADP in rat serum and adipose tissue, the serum TC, TG, HDL-C and LDL-C, the mRNA and protein expression levels of lipid metabolism-related gene CEBP/ß and inflammation-related gene CD68 were measured. RESULTS: After exposure to DEHP, the weight of rats in the high dose group was significantly higher than that in the control group (p < 0.05). And the number of adipose tissue cells in the medium-dose and high-dose DEHP groups increased, with much more macrophage infiltrated. The levels of LDL-C, HDL-C, TC in serum and LEP in adipose tissue of rats exposed to 500 mg/kg DEHP were significantly higher than those in the control group (p < 0.05); while the level of ADP in adipose tissue in rats exposed to DEHP was significantly lower (p < 0.05). The levels of IL-1ß and TNF-α in surum and adipose tissue of rats exposed to DEHP were significantly higher than those in the control group (p < 0.05). The mRNA and protein expression levels of CEBP/ß and CD68 in adipose tissue of rats exposed to DEHP were significantly higher than those in the control group. The TC, LEP and ADP Levels of rats were significantly different among different subgroup of IL-1ß and TNF-α, and in high level subgroup, the TC, LEP and ADP Levels were increased. The levels of TC and LEP was increased in high level subgroup of CD68. CONCLUSION: DEHP induced more macrophage infiltrated in adipose tissue of rats, promoted the secretion of IL-1ß, TNF-α and the formation of inflammation, and disturbed the normal lipid metabolism and lead to lipid metabolic disorders. What is more, the levels of inflammation were associated with the lipid levels.


Assuntos
Dietilexilftalato/toxicidade , Inflamação/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/sangue , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/sangue , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Peso Corporal , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Interleucina-1beta/sangue , Leptina/sangue , Masculino , Doenças Metabólicas/induzido quimicamente , Ratos , Ratos Wistar , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue
19.
Nucleic Acids Res ; 47(4): 1774-1785, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30566668

RESUMO

CCAAT/enhancer binding proteins (C/EBPs) regulate gene expression in a variety of cells/tissues/organs, during a range of developmental stages, under both physiological and pathological conditions. C/EBP-related transcription factors have a consensus binding specificity of 5'-TTG-CG-CAA-3', with a central CpG/CpG and two outer CpA/TpG dinucleotides. Methylation of the CpG and CpA sites generates a DNA element with every pyrimidine having a methyl group in the 5-carbon position (thymine or 5-methylcytosine (5mC)). To understand the effects of both CpG and CpA modification on a centrally-important transcription factor, we show that C/EBPß binds the methylated 8-bp element with modestly-increased (2.4-fold) binding affinity relative to the unmodified cognate sequence, while cytosine hydroxymethylation (particularly at the CpA sites) substantially decreased binding affinity (36-fold). The structure of C/EBPß DNA binding domain in complex with methylated DNA revealed that the methyl groups of the 5mCpA/TpG make van der Waals contacts with Val285 in C/EBPß. Arg289 recognizes the central 5mCpG by forming a methyl-Arg-G triad, and its conformation is constrained by Val285 and the 5mCpG methyl group. We substituted Val285 with Ala (V285A) in an Ala-Val dipeptide, to mimic the conserved Ala-Ala in many members of the basic leucine-zipper family of transcription factors, important in gene regulation, cell proliferation and oncogenesis. The V285A variant demonstrated a 90-fold binding preference for methylated DNA (particularly 5mCpA methylation) over the unmodified sequence. The smaller side chain of Ala285 permits Arg289 to adopt two alternative conformations, to interact in a similar fashion with either the central 5mCpG or the TpG of the opposite strand. Significantly, the best-studied cis-regulatory elements in RNA polymerase II promoters and enhancers have variable sequences corresponding to the central CpG or reduced to a single G:C base pair, but retain a conserved outer CpA sequence. Our analyses suggest an important modification-dependent CpA recognition by basic leucine-zipper transcription factors.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/química , Metilação de DNA/genética , Proteínas de Ligação a DNA/química , DNA/genética , 5-Metilcitosina/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Sequência Conservada/genética , Ilhas de CpG/genética , Cristalografia por Raios X , Citosina/metabolismo , Proteínas de Ligação a DNA/genética , Elementos E-Box/genética , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Conformação Proteica , Timina/metabolismo , Fator de Transcrição AP-1/química , Fator de Transcrição AP-1/genética
20.
J Oral Sci ; 60(4): 601-610, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30587692

RESUMO

Follicular dendritic cell-secreted protein (FDC-SP) is expressed in FDCs, human periodontal ligament (HPL) cells, and junctional epithelium. To evaluate the effects of interleukin-1 beta (IL-1ß) on FDC-SP gene expression in immortalized HPL cells, FDC-SP mRNA and protein levels in HPL cells following stimulation by IL-1ß were measured by real-time polymerase chain reaction and Western blotting. Luciferase (LUC), gel mobility shift, and chromatin immunoprecipitation (ChIP) analyses were performed to study the interaction between transcription factors and promoter regions in the human FDC-SP gene. IL-1ß (1 ng/mL) induced the expression of FDC-SP mRNA and protein levels at 3 h, and reached maximum levels at 12 h. IL-1ß increased LUC activities of constructs (-116FDCSP - -948FDCSP) including the FDC-SP gene promoter. Transcriptional inductions by IL-1ß were partially inhibited by 3-base-pair (3-bp) mutations in the Yin Yang 1 (YY1), GATA, CCAAT-enhancer-binding protein2 (C/EBP2), or C/EBP3 in the -345FDCSP. IL-1ß-induced -345FDCSP activities were inhibited by protein kinase A, tyrosine-kinase, mitogen-activated protein kinase (MEK)1/2, and PI3-kinase inhibitors. The results of gel shift and ChIP assays revealed that YY1, GATA, and C/EBP-ß interacted with the YY1, GATA, C/EBP2, and C/EBP3 elements that were increased by IL-1ß. These studies demonstrate that IL-1ß increases FDC-SP gene transcription in HPL cells by targeting YY1, GATA, C/EBP2, and C/EBP3 in the human FDC-SP gene promoter.


Assuntos
Células Dendríticas Foliculares/metabolismo , Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/farmacologia , Ligamento Periodontal/citologia , Proteínas/metabolismo , Western Blotting , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Células Cultivadas , Inserção Epitelial/metabolismo , Fatores de Transcrição GATA/genética , Fatores de Transcrição GATA/metabolismo , Humanos , Imunoprecipitação , Regiões Promotoras Genéticas , Proteínas/genética , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Genética , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
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