Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.419
Filtrar
1.
Adv Clin Exp Med ; 28(10): 1293-1300, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31538414

RESUMO

BACKGROUND: MicroRNA (miRNA) is a kind of non-coding small RNA with a negative regulating function. Some miRNAs play a role in regulating the differentiation and function of osteoblasts, chondrocytes and osteoclasts. OBJECTIVES: In this study, we analyzed the role of miR-29a and dickkopf-1 (DKK-1) in osteoblast differentiation. MATERIAL AND METHODS: Specimens were collected from the surgical resection of pathological ankylosing spondylitis (AS) tissue and some normal tissues. The expression of miR-29a, DKK-1 and ß-catenin in normal and AS tissues were detected with real-time polymerase chain reaction (RT-PCR) and western blotting. Cell proliferation was detected with a Cell Counting Kit-8, cell migration and invasion were determined using a Transwell system and cell apoptosis was analyzed with flow cytometry. The luciferase reporter gene plasmid pGL3-DKK-1 and a point-mutation of the luciferase reporter gene plasmid mut-pGL3-DKK-1 were constructed. RESULTS: It was found that miR-29a could promote the proliferation of hFOB1.19 cells, while DKK-1 inhibited their proliferation. Also, miR-29a was able to inhibit the apoptosis of hFOB1.19 cells, while DKK-1 was able to promote the apoptosis of hFOB1.19 cells. When it comes to the invasion and migration of hFOB1.19 cells, miR-29a was found to promote it, while DKK-1 did not. CONCLUSIONS: These findings will lead to a better understanding of the proliferation and differentiation of osteoblasts and will provide new insights for the treatment of this disease.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Via de Sinalização Wnt/fisiologia , Apoptose/fisiologia , Proliferação de Células , Humanos , MicroRNAs/genética , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
2.
Oncology ; 97(5): 311-318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31550723

RESUMO

INTRODUCTION: Human epidermal growth factor 2 (HER2) gene overexpression in breast carcinoma cell lines has been shown to drive mammary carcinogenesis and tumor growth and invasion through its effects on mammary stem cells. OBJECTIVE: Therefore, we investigated the mechanism by which HER2 regulates cancer stem cell (CSC) activity in gastric cancer cells. METHODS: HER2 was transfected into MKN28 gastric cancer cells, and its role in regulating CSC activity was determined by characterizing the HER2-overexpressing cells. RESULTS: The sphere formation assay revealed that the sphere sizes and frequency of sphere formation were significantly greater for the HER2-overexpressing cells than for the MKN28 control cells. The CSC markers Oct-4 and BMI1 were more highly expressed in the HER2-overexpressing cells, as were the EMT markers. This was accompanied by a significant enhancement in cellular invasion of the Matrigel and migration. The E-cadherin level was significantly downregulated, and the mesenchymal marker Snail upregulated, in the HER2-transfected cells. HER2 overexpression activated the well-characterized CSC-associated Wnt/ß-catenin signaling pathway, as shown by the luciferase assay. After treatment of these cells with the Wnt signal inhibitor PRI-724, the BMI1 and Oct-4 levels were decreased for 24 h and Snail was also downregulated. Immunofluorescence staining revealed the significant restoration of E-cadherin levels in the HER2-transfected cells after PRI-724 treatment. CONCLUSIONS: These results established a role for HER2 in regulating gastric CSC activity, with Wnt/ß-catenin signaling being mediated via a HER2-dependent pathway. In summary, HER2-overexpressing gastric cancer cells exhibited increased stemness and invasiveness and were regulated by Wnt/ß-catenin signaling.


Assuntos
Células-Tronco Neoplásicas/fisiologia , Receptor ErbB-2/fisiologia , Neoplasias Gástricas/patologia , Via de Sinalização Wnt/fisiologia , Antígenos CD/análise , Caderinas/análise , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Fator 3 de Transcrição de Octâmero/análise , Complexo Repressor Polycomb 1/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/química , beta Catenina/análise
3.
Acta Cir Bras ; 34(5): e201900502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166463

RESUMO

PURPOSE: To investigate inhibitory effect of Astragalus polysaccharide (APS) on osteoporosis in ovariectomized rats by regulating FoxO3a/Wnt2 signaling pathway. METHODS: Postmenopausal osteoporosis (PMOP) animal model was developed by excising the bilateral ovaries of rats. The model rats were administered with APS (200 mg/kg, 400 mg/kg, 800 mg/kg) by intragastric administration once daily for 12 weeks. Bone density, bone metabolism index and oxidative stress index were measured in all groups. Furthermore, the regulation of APS of FoxO3a / Wnt2 signaling pathway was observed. RESULTS: APS has an estrogen-like effect, which can increase bone mass, lower serum ALP and BGP values, increase blood calcium content, and increase bone density of the femur and vertebrae in rats. At the same time, APS can increase the bone mineral content of the femur, increase the maximum stress, maximum load and elastic modulus of the ovariectomized rats, improve oxidative stress in rats by increasing the gene expression of ß-catenin and Wnt2 mRNA and inhibiting the gene expression of FoxO3a mRNA. CONCLUSION: Astragalus polysaccharide can effectively alleviate oxidative stress-mediated osteoporosis in ovariectomized rats, which may be related to its regulation of FoxO3a/Wnt2/ß-catenin pathway.


Assuntos
Astrágalo (Planta)/química , Proteína Forkhead Box O3/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Polissacarídeos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Proteína Forkhead Box O3/análise , Expressão Gênica/efeitos dos fármacos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/efeitos dos fármacos , Osteoporose/metabolismo , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Reprodutibilidade dos Testes , Resultado do Tratamento , Via de Sinalização Wnt/fisiologia , Proteína Wnt2/análise , Proteína Wnt2/efeitos dos fármacos , beta Catenina/análise , beta Catenina/efeitos dos fármacos
4.
Nat Cell Biol ; 21(7): 812-823, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235935

RESUMO

Wnt signalling stimulated by binding of R-spondin (Rspo) to Lgr-family members is crucial for gastrointestinal stem cell renewal. Infection of the stomach with Helicobacter pylori stimulates increased secretion of Rspo by myofibroblasts, leading to an increase in proliferation of Wnt-responsive Axin2+Lgr5- stem cells in the isthmus of the gastric gland and finally gastric gland hyperplasia. Basal Lgr5+ cells are also exposed to Rspo3, but their response remains unclear. Here, we demonstrate that-in contrast to its known mitogenic activity-Rspo3 induces differentiation of basal Lgr5+ cells into secretory cells that express and secrete antimicrobial factors, such as intelectin-1, into the lumen. The depletion of Lgr5+ cells or the knockout of Rspo3 in myofibroblasts leads to hypercolonization of the gastric glands with H. pylori, including the stem cell compartment. By contrast, systemic administration or overexpression of Rspo3 in the stroma clears H. pylori from the gastric glands. Thus, the Rspo3-Lgr5 axis simultaneously regulates both antimicrobial defence and mucosal regeneration.


Assuntos
Mucosa Gástrica/metabolismo , Trombospondinas/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Autorrenovação Celular/fisiologia , Camundongos Transgênicos , Miofibroblastos/metabolismo , Organoides/citologia , Receptores Acoplados a Proteínas-G/genética , Células-Tronco/metabolismo , Estômago/efeitos dos fármacos , Trombospondinas/genética , Trombospondinas/farmacologia , Via de Sinalização Wnt/fisiologia
5.
Curr Protein Pept Sci ; 20(8): 829-843, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31060486

RESUMO

Inflammation is the first response occurring after damage or infection, which is a defensive process for the body. It is well known that excessive inflammation can lead to further diseases such as fibrosis. But a regenerative inflammatory response can accelerate the process of repairing injury, in which a variety of cytokines, immune cells, and stem cells are involved. The Wnt signaling pathway was originally known in the field of development. Recently, its role in regenerative inflammation has gradually been established. Wnt signaling can regulate cell proliferation and differentiation through regulating participants of regenerative inflammation. Canonical and noncanonical Wnt signaling pathways are coordinated to maintain homeostasis. Based on the process of regenerative inflammation and recent research in this field, this paper reviews how the Wnt signaling pathway interact with other cells and pathways.


Assuntos
Inflamação/metabolismo , Regeneração/fisiologia , Via de Sinalização Wnt/fisiologia , Cicatrização/fisiologia , Animais , Citocinas/metabolismo , Humanos
6.
Ren Fail ; 41(1): 159-166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30931679

RESUMO

Intermedin (IMD) is a member of the calcitonin gene-related peptide (CGRP) superfamily and a pro-angiogenic factor. In the present study, we identified activation of the Wnt/ß-catenin signaling pathway by IMD. Adding CoCl2 HUVECs was used to establish an in vitro model. The migration of HUVECs was measured by wound healing assays and transwell migration assays. Capillary formation was measured using tube formation assays. Immunocytochemistry (ICC) analysis was used to evaluate VEGF and RAMP2 expression in HUVECs. The relevant signaling molecules were detected with western blot. Our study shows that IMD could promote H/R impaired HUVECs migration and tube formation in vitro. On the other hand, inhibition of Wnt/ß-catenin signaling led to the suppression of this promotion of migration and tube formation. This result suggests that Wnt/ß-catenin signaling is correlated to IMD induced angiogenesis. Analysis of results from ICC assays indicated that IMD works through increasing levels of VEGF and RAMP2. Meanwhile, the Wnt/ß-catenin signaling specific inhibitor IWR-1-endo was shown to down-regulate VEGF and RAMP2 expression. Western blot results further confirmed the signaling mechanism by which IMD promotes angiogenesis. Thus, Wnt/ß-catenin signaling plays an important role in IMD induced neovascularization. The data further suggest that the PI3K axis contributes positively downstream.


Assuntos
Neovascularização Fisiológica , Hormônios Peptídicos/metabolismo , Traumatismo por Reperfusão/patologia , Via de Sinalização Wnt/fisiologia , Linhagem Celular , Cobalto/toxicidade , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Imidas/farmacologia , Quinolinas/farmacologia , Proteína 2 Modificadora da Atividade de Receptores/metabolismo , Traumatismo por Reperfusão/induzido quimicamente , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
7.
Nat Commun ; 10(1): 1804, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31000703

RESUMO

Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we develop the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein kinase 1 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1ɛ in DVL conformational dynamics.


Assuntos
Caseína Quinase Iépsilon/metabolismo , Proteínas Desgrenhadas/metabolismo , Domínios PDZ/fisiologia , Via de Sinalização Wnt/fisiologia , Animais , Técnicas Biossensoriais , Caseína Quinase Iépsilon/genética , Proteínas Desgrenhadas/genética , Ensaios Enzimáticos/métodos , Transferência Ressonante de Energia de Fluorescência , Receptores Frizzled/metabolismo , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Microscopia de Fluorescência/métodos , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Oócitos , Fosforilação/fisiologia , Análise de Célula Única/métodos , Xenopus laevis
8.
ScientificWorldJournal ; 2019: 4714781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30940992

RESUMO

For gastrulation to occur in human embryos, a mechanism that simultaneously regulates many different processes, such as cell differentiation, proliferation, migration, and invasion, is required to consistently and effectively create a human being during embryonic morphogenesis. The striking similarities in the processes of cancer and gastrulation have prompted speculation regarding the developmental pathways involved in their regulation. One of the fundamental requirements for the developmental pathways in gastrulation and cancer is the ability to respond to environmental stimuli, and it has been proposed that the Kaiso and noncanonical Wnt pathways participate in the mechanisms regulating these developmental pathways. In particular, these pathways might also explain the notable differences in invasive capacity between cancers of endodermal and mesodermal origins and cancers of ectodermal origin. Nevertheless, the available information indicates that cancer is an abnormal state of adult human cells in which developmental pathways are reactivated in inappropriate temporal and spatial contexts.


Assuntos
Modelos Biológicos , Neoplasias/metabolismo , Via de Sinalização Wnt/fisiologia , Diferenciação Celular , Movimento Celular , Epigênese Genética , Gastrulação , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Neoplasias/genética , Proteínas Wnt/metabolismo
9.
Biomed Pharmacother ; 114: 108825, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981110

RESUMO

Large tumor suppressor 2 (LATS2), an important mediator of the cell apoptotic response pathway, has been linked to the progression of several cancers. Here, we described the molecular feature of LATS2 as a novel antitumor factor in liver cancer cells in vitro. Western blotting was used to detect the expression of LATS2 and its downstream factors. ELISA, immunofluorescence, and flow cytometry were used to evaluate the alterations of mitochondrial function in response to LATS2 overexpression. Adenovirus-loaded LATS2 and siRNA against DRP1 were transfected into liver cancer cells to overexpress LATS2 and knockdown DRP1 expression, respectively. The results of the present study demonstrated that overexpression of LATS2 was closely associated with more liver cancer cell death. Mechanistically, LATS2 overexpression increased the expression of DRP1, and DRP1 elevated mitochondrial division, an effect that was accompanied by mitochondrial dysfunction, including mitochondrial membrane potential reduction, mitochondrial respiratory complex downregulation, mitochondrial cyt-c release into the nucleus and mitochondrial oxidative injury. Moreover, LATS2 overexpression also initiated mitochondrial apoptosis, and this process was highly dependent on DRP1-related mitochondrial division. Molecular investigations demonstrated that LATS2 modulated DRP1 expression via the Wnt/ß-catenin pathway. Inhibition of the Wnt/ß-catenin pathway pregented LATS2-mediated DRP1 upregulation, ultimately sustaining mitochondrial function and cell viability in the presence of LATS2 overexpression. Altogether, the above data identify LATS2-Wnt/ß-catenin/DRP1/mitochondrial division as a novel anticancer signaling pathway promoting cancer cell death, which might be an attractive therapeutic target for the treatment of hepatocellular carcinoma.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Via de Sinalização Wnt/fisiologia , Apoptose/fisiologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Regulação para Baixo/fisiologia , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia , beta Catenina/metabolismo
10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(2): 134-139, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30975277

RESUMO

Objective To explore the relationship between the drug resistance gene ATP binding cassette sub-family B member 4 (abcb4) in zebrafish and Wnt/ß-catenin signaling pathway. Methods Wild-type zebrafish and transgenic zebrafish were set in the blank control group, doxorubicin treatment group, vinblastine treatment group, gefitinib treatment group, doxorubicin combined with gefitinib treatment group, and vinblastine combined with gefitinib treatment group. The 100 embryos of each group were treated with drugs until the 5th day, and 50 zebrafish juveniles were tested on the 5th day in each group. The drug resistance of wild-type zebrafish was tested by rhodamine 123 experiment. The fluorescence intensity of transgenic zebrafish was tested by microplate reader, and the fluorescence distribution was tested by living cell workstation. The protein levels of transgenic zebrafish ß-catenin, GSK-3ß, ABCB4 and enhanced green fluorescent protein (EGFP) were tested by Western blot analysis. Results Rhodamine 123 experiments proved that there was drug resistance in zebrafish when treated with doxorubicin and vinblastine. Compared with the blank group, the EGFP fluorescence intensity increased in the transgenic zebrafish when treated with doxorubicin and vinblastine. Western blot assay showed the accumulation of ß-catenin accompanied by the increase of EGFP and ABCB4 proteins in the transgenic zebrafish exposed to adriamycin and vincristine. Conclusion The Wnt/ß-catenin signaling pathway in zebrafish is involved in the activation and drug resistance of zebrafish abcb4 gene.


Assuntos
Resistência a Medicamentos , Via de Sinalização Wnt , Proteínas de Peixe-Zebra , Peixe-Zebra , beta Catenina , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Animais Geneticamente Modificados , Antineoplásicos/farmacologia , Resistência a Medicamentos/genética , Embrião não Mamífero/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Proteínas de Peixe-Zebra/genética , beta Catenina/metabolismo
11.
DNA Cell Biol ; 38(5): 410-422, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896984

RESUMO

Trophoblast stem cells (TSCs), the precursors of placental cells, are effective for studying placental formation in vitro. Using a dual inhibition (2i) medium and mixed L-Wnt3a/mouse embryonic fibroblast feeder cells, we previously established the bovine trophoblast cell line BTS-1. In this study, we used bovine fetal fibroblasts and added Wnt3a to the 2i medium to establish another bovine TSC line (BTSW). BTSW cells expressed pluripotency markers, including NANOG, SOX2, OCT4, TRA-1-60, TRA-1-81, SSEA4, CDH1, and KRT18, and TSC markers CDX2, TEAD4, and ESRRB. Methylation sequencing of the promoter regions of NANOG, OCT4, and CDX2 revealed no significant differences between BTS-1 and BTSW cells. Removal of Wnt3a from the culture medium resulted in downregulation (p < 0.05) of NANOG, OCT4, CDX2, and TSC marker genes, and upregulation of TSC differentiation markers, including MASH2, GCM1, and PAG. Western blotting indicated activation of the WNT-YAP/TAZ signaling pathway in BTS-1 and BTSW cells, consequently activating TEAD4 transcription. However, this pathway was not activated in BCFF cells, an established bovine embryonic stem-like cell line that expresses OCT4, SOX2, and NANOG, but not CDX2. Thus, Wnt3a may play a critical role in bovine TSC maintenance by activating and regulating CDX2 expression through the WNT-YAP/TAZ signaling pathway.


Assuntos
Fator de Transcrição CDX2/metabolismo , Células-Tronco Embrionárias/citologia , Fator 3 de Transcrição de Octâmero/genética , Trofoblastos/citologia , Via de Sinalização Wnt/fisiologia , Proteína Wnt3/metabolismo , Animais , Fator de Transcrição CDX2/genética , Bovinos , Linhagem Celular , Linhagem da Célula
12.
Drug Discov Ther ; 13(1): 22-27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880318

RESUMO

This study was done with aim to assess the serum sclerostin and dickkopf-1 (DKK-1) level in patients of rheumatoid arthritis (RA) and to correlate their level with disease activity and bone mineral density. Fifty patients of RA and equal age and sex matched healthy controls were included in the study. Patients were evaluated clinically and investigated with routine blood tests along with rheumatoid factor (RF), anti-citrullinated protein antibody (anti-CCP2), radiographs and bone mineral density (BMD). Serum sclerostin and DKK-1 levels of both cases and controls was assayed by using enzyme-linked immunosorbent assay (ELISA) assay [RayBio®, Georgia, USA with coefficient of variation percent (CV %), < 10%] and compared with disease activity and bone mineral density. Disease activity was measured by Disease Activity Score 28 (DAS28) along with Modified Health Assessment Questionnaire (MHAQ) score. Mean serum sclerostin and DKK-1 was significantly higher in study group as compared to control group. Serum sclerostin showed significant correlation with disease activity scores (DAS score and MHAQ score), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Serum sclerostin at level of 394 pg/mL was found to have diagnostic significance with sensitivity of 100% and specificity of 90%. DKK-1 level shows significantly positive correlation with larson score which denotes radiological progression (r value 0.468; p value 0.001). More studies with larger sample size of RA patients are needed for better determination of the role of sclerostin and DKK-1 in RA. Also, the correlation of these and other bone turn over markers will help decipher their role with disease progression in RA patients.


Assuntos
Artrite Reumatoide/metabolismo , Proteínas Morfogenéticas Ósseas/biossíntese , Remodelação Óssea/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Índice de Gravidade de Doença , Via de Sinalização Wnt/fisiologia , Adulto , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/genética , Densidade Óssea/fisiologia , Proteínas Morfogenéticas Ósseas/genética , Estudos de Casos e Controles , Feminino , Expressão Gênica , Marcadores Genéticos/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
J Craniofac Surg ; 30(3): 703-708, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30839467

RESUMO

Grafts and prosthetic materials used for the repair of bone defects are often accompanied by comorbidity and rejection. Therefore, there is an immense need for novel approaches to combating the issues surrounding such defects. Because of their accessibility, substantial proportion, and osteogenic differentiation potential, adipose-derived stem cells (ASCs) make for an ideal source of bone tissue in regenerative medicine. However, efficient induction of ASCs toward an osteoblastic lineage in vivo is met with challenges, and many signaling pathways must come together to secure osteoblastogenesis. Among them are bone morphogenic protein, wingless-related integration site protein, Notch, Hedgehog, fibroblast growth factor, vascular endothelial growth factor, and extracellular regulated-signal kinase. The goal of this literature review is to conglomerate the present research on these pathways to formulate a better understanding of how ASCs are most effectively transformed into bone in the context of tissue engineering.


Assuntos
Osteogênese/fisiologia , Células-Tronco/citologia , Adipócitos/metabolismo , Tecido Adiposo/citologia , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Regulação para Baixo , Fatores de Crescimento de Fibroblastos/fisiologia , Proteínas Hedgehog/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Osteoblastos/citologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt/fisiologia
14.
Ying Yong Sheng Tai Xue Bao ; 30(1): 37-42, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30907523

RESUMO

Chronic fluoride-arsenic combined poisoning is a global public health problem. While the cause of the disease is clear, the pathogenesis is unknown. Given that there is no specific treatment, early prevention is particularly important. Biological exposure limits are designed to investigate the maximum allowable concentration of harmful effects from exogenous chemicals. To explore the biological exposure limits for mixed exposures of fluoride and arsenic, we compared the contents of fluorine and arsenic in the environmental media of the control and fluoride-arsenic combined exposure areas and analyzed the dose-effect and dose-response relationship between fluoride, arsenic and the key proteins of Wnt signaling pathways. The benchmark dose method was used to estimate the biological exposure limit for fluoride-arsenic combined exposure. The results showed that the content of fluoride in coal, clay, indoor air, outdoor air, chili and rice, as well as arsenic content in coal, clay, outdoor air, chili and rice was higher than that of the control. With the increase of fluoride and arsenic exposure levels, the glycogen synthase kinase 3β (GSK3β), β-catenincontents and the prevalence of Wnt/β-catenin signaling pathway antagonistic protein Dickkopf-1 (DKK1), GSK3β, Beta-catenin (β-catenin) gradually increased, but the content of DKK1 significantly decreased. Based on the Wnt signaling pathway, the biological exposure limit for fluoride-arsenic combined exposure was urinary fluoride of 0.52 mg·g-1 creatinine and urinary arsenic of 6.59 mg·g-1 creatinine. Our results had important guiding significance for early prevention of body damage caused by fluoride-arsenic combined poisoning.


Assuntos
Arsênico/metabolismo , Exposição Ambiental/estatística & dados numéricos , Fluoretos/metabolismo , Poluentes Químicos da Água/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Arsênico/toxicidade , Carvão Mineral , Fluoretos/toxicidade , Minerais , Poluentes Químicos da Água/toxicidade , Via de Sinalização Wnt/fisiologia
15.
An Acad Bras Cienc ; 91(1): e20180459, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30916158

RESUMO

This study aimed to investigate how 6-bromoindirubin-3'-oxime (BIO) increases the osteogenic differentiation of canine bone mesenchymal stem cells (BMSCs) and the role of the Wnt/ß-catenin signaling pathway in this process. We mimicked the effect of Wnt by adding BIO to the culture medium of BMSCs and examined whether canonical Wnt signaling positively affects the differentiation of these cells into osteoblasts. Canine BMSCs were cultured with 0.5 and 1.0 µM BIO under osteogenic conditions and then differentiation markers were investigated. It was found that BIO significantly increased the activity of alkaline phosphatase (ALP), the number of ALP-positive cells, the mineralization level and calcium deposits. Moreover, cells cultured with 0.5 and 1.0 µM BIO exhibited detectable ß-catenin expression in their nuclei, and showed upregulated ß-catenin and glycogen synthase kinase 3 beta(GSK3ß) phosphorylation compared to untreated cells. In addition, BIO enhanced the mRNA expression of osteoblast differentiation markers such as ALP, runt-related transcription factor 2, collagen I, osteocalcin, and osteonectin. In conclusion, BIO upregulated GSK3ß phosphorylation and inhibited its activity, thereby activating the Wnt/ß-catenin signaling pathway and promoting the osteogenic differentiation of canine BMSCs. The effect of 1.0 µM BIO on BMSCs differentiation was stronger than that of 0.5 µM BIO.


Assuntos
Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Indóis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Oximas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/metabolismo , Cães , Indóis/uso terapêutico , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteogênese/genética , Osteogênese/fisiologia , Oximas/uso terapêutico , Transdução de Sinais , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/fisiologia
16.
PLoS Genet ; 15(3): e1008054, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30925162

RESUMO

Wnt/ß-catenin signaling is an ancient pathway in metazoans and controls various developmental processes, in particular the establishment and patterning of the embryonic primary axis. In vertebrates, a graded Wnt activity from posterior to anterior endows cells with positional information in the central nervous system. Recent studies in hemichordates support a conserved role for Wnt/ß-catenin in ectoderm antero-posterior patterning at the base of the deuterostomes. Ascidians are marine invertebrates and the closest relatives of vertebrates. By combining gain- and loss-of-function approaches, we have determined the role of Wnt/ß-catenin in patterning the three ectoderm derivatives of the ascidian Ciona intestinalis, central nervous system, peripheral nervous system and epidermis. Activating Wnt/ß-catenin signaling from gastrulation led to a dramatic transformation of the ectoderm with a loss of anterior identities and a reciprocal anterior extension of posterior identities, consistent with studies in other metazoans. Surprisingly, inhibiting Wnt signaling did not produce a reciprocal anteriorization of the embryo with a loss of more posterior identities like in vertebrates and hemichordate. Epidermis patterning was overall unchanged. Only the identity of two discrete regions of the central nervous system, the anteriormost and the posteriormost regions, were under the control of Wnt. Finally, the caudal peripheral nervous system, while being initially Wnt dependent, formed normally. Our results show that the Ciona embryonic ectoderm responds to Wnt activation in a manner that is compatible with the proposed function for this pathway at the base of the deuterostomes. However, possibly because of its fast and divergent mode of development that includes extensive use of maternal determinants, the overall antero-posterior patterning of the Ciona ectoderm is Wnt independent, and Wnt/ß-catenin signaling controls the formation of some sub-domains. Our results thus indicate that there has likely been a drift in the developmental systems controlling ectoderm patterning in the lineage leading to ascidians.


Assuntos
Padronização Corporal/fisiologia , Urocordados/crescimento & desenvolvimento , Via de Sinalização Wnt/fisiologia , Animais , Padronização Corporal/genética , Ciona intestinalis/crescimento & desenvolvimento , Ciona intestinalis/metabolismo , Ectoderma/metabolismo , Ectoderma/fisiologia , Gastrulação , Regulação da Expressão Gênica no Desenvolvimento/genética , Transdução de Sinais , Urocordados/genética , Urocordados/metabolismo , Vertebrados , Proteínas Wnt
17.
Physiol Int ; 106(1): 1-20, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30917670

RESUMO

In the past decade, researches on Wnt signaling in cell biology have made remarkable progress regarding our understanding of embryonic development, bone formation, muscle injury and repair, neurogenesis, and tumorigenesis. The study also showed that physical activity can reverse age-dependent decline in skeletal muscle, preventing osteoporosis, regenerative neurogenesis, hippocampal function, cognitive ability, and neuromuscular junction formation, and the age-dependent recession is highly correlated with Wnt signaling pathways. However, how the biological processes in cell and physical activity during/following exercise affect the Wnt signaling path of the locomotor system is largely unknown. In this study, we first briefly introduce the important features of the cellular biological processes of exercise in the locomotor system. Then, we discuss Wnt signaling and review the very few studies that have examined Wnt signaling pathways in cellular biological processes of the locomotor system during physical exercise.


Assuntos
Exercício/fisiologia , Músculo Esquelético/metabolismo , Junção Neuromuscular/metabolismo , Condicionamento Físico Animal/fisiologia , Via de Sinalização Wnt/fisiologia , Animais , Encéfalo/metabolismo , Humanos
18.
J Exp Clin Cancer Res ; 38(1): 104, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30813948

RESUMO

BACKGROUND: Tripartite Motif 29 (TRIM29) has been newly identified as being implicated in cancer progression. However, the biological role and molecular mechanism of TRIM29 in the invasion and metastasis of colorectal cancer (CRC) remain to be determined. METHODS: The expression levels of TRIM29 and ß-catenin in CRC patient specimens were detected by immunohistochemistry. Recombinant lentivirus vectors containing the TRIM29 gene and its small hairpin interfering RNAs were constructed and transduced into CRC cells. Wound-healing and Transwell assays were performed to evaluate the migration and invasion abilities of CRC cells in vitro. Hepatic metastasis models in nude mice were established to validate the function of TRIM29 in vivo. Moreover, the expressions of epithelial-to-mesenchymal transition (EMT)-associated proteins were detected by qRT-PCR and Western blotting in CRC cells. Finally, Western blotting, qRT-PCR, luciferase reporter assays, and immunofluorescence assays were used to explore the molecular mechanisms of TRIM29 in CRC progression. RESULTS: Increased TRIM29 expression positively correlated with lymph node metastasis and ß-catenin expression in patient CRC tissues. Overexpression of TRIM29 promoted invasion and metastasis of CRC cells in vitro and in vivo by regulating EMT, whereas the knockdown of TRIM29 had the opposite effect. Further mechanistic studies suggest that TRIM29 can activate the Wnt/ß-catenin signaling pathway via up-regulating CD44 expression in colorectal cancer. CONCLUSIONS: TRIM29 induces EMT through activating the Wnt/ß-catenin signaling pathway via up-regulating CD44 expression, thus promoting invasion and metastasis of CRC.


Assuntos
Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Receptores de Hialuronatos/biossíntese , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt/fisiologia , Adulto , Idoso , Animais , Movimento Celular/fisiologia , Neoplasias Colorretais/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia
19.
Clin Calcium ; 29(3): 283-289, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30814372

RESUMO

The Wnt signaling pathways are classified into the ß-catenin dependent pathway, which regulates gene expression through ß-catenin, and the ß-catenin independent pathway, which does cytoskeletal rearrangement in a ß-catenin independent manner. The former is also called as the canonical Wnt signaling pathway and extensively studied in development, tumorigenesis, and regenerative research. Recently, novel mechanistic insights into the canonical Wnt signaling pathway have been clarified through the analysis of structure of Wnt-receptor complex, regulation of Wnt signaling at the cell surface membrane, and intracellular protein complex of Wnt complexes.


Assuntos
Via de Sinalização Wnt , beta Catenina , Humanos , Via de Sinalização Wnt/fisiologia , beta Catenina/genética , beta Catenina/metabolismo
20.
Life Sci ; 220: 84-91, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710639

RESUMO

A number of evidences suggest that microRNAs are involved in the adipogenic commitment of mesenchymal stem cells (MSCs). Recent studies have investigated that miR-199a-3p played a pivotal role in adipocyte differentiation. However, the detailed mechanism in this complex biological process remains largely unknown. In current study, we found that the expression of miR-199a-3p was gradually increased during adipogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs). Enhanced expression of miR-199a-3p promoted adipogenesis, whereas silence of miR-199a-3p rescued BMMSCs from adipogenic commitment. For further mechanism exploration, KDM6A was confirmed to be the target of miR-199a-3p and the expression of KDM6A was gradually decreased during adipogenic differentiation of BMMSCs. Furthermore, up-regulation of KDM6A markedly abolished the miR-199a-3p overexpression induced adipogenic augmentation, whereas down-regulation of KDM6A suppressed the adipogenic reduction caused by miR-199a-3p silence. In addition, WNT signaling was also verified to be the downstream of miR-199a-3p/KDM6A to regulate adipogenic differentiation of BMMSCs. Taken together, current results indicate that miR-199a-3p regulate adipogenesis of BMMSCs by targeting KDM6A/WNT signaling, which highlights a new insight for a better understanding of molecular mechanism and stem cell based therapy on osteoporotic diseases.


Assuntos
Adipogenia/genética , Histona Desmetilases/metabolismo , MicroRNAs/fisiologia , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/patologia , Diferenciação Celular/genética , Células Cultivadas , Regulação para Baixo , Feminino , Histona Desmetilases/genética , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Regulação para Cima , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA