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1.
Zhonghua Nei Ke Za Zhi ; 59(1): 58-61, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31887838

RESUMO

The purpose of this study is to investigate the matrix metalloproteinase-3 (MMP-3) levels in patients with systemic lupus erythematosus (SLE) and its significance in identifying disease activity and pulmonary infections. A total of 122 SLE patients were enrolled, including 21 with pulmonary infections, 16 with arthritis, 26 with nephritis, 10 with vasculitis, and 23 healthy controls. Serum MMP-3, C-reactive protein (CRP), serum amyloid A (SAA), and haptoglobin (HPT) levels were measured in all subjects. The results showed that the levels of MMP-3 in SLE combined with pulmonary infections [(230.10±44.92) µg/L], arthritis [(140.20±20.76) µg/L], nephritis [(155.40±23.36) µg/L] were higher than those in SLE only [(91.74±10.47) µg/L]. The levels of MMP-3 [(210.30±45.71) µg/L], CRP [(12.11±5.21) mg/L], HPT [(1.57±0.23) g/L] in active SLE combined with pulmonary infections were higher than those inactive SLE without pulmonary infections including MMP-3 [(124.00±15.22) µg/L], CRP [(7.76±2.96) mg/L], HPT [(0.89±0.09) g/L]. The levels of CRP [(10.03±2.70) mg/L], SAA [(89.22±36.77) mg/L] in active SLE with pulmonary infections and CRP[(7.76±2.96) mg/L], SAA [(60.22±19.7) mg/L] in active SLE without pulmonary infections were higher than CRP [(1.90±0.39) mg/L], SAA [(17.60±3.89) mg/L] in stable SLE with pulmonary infections. It suggests that the levels of CRP and SAA are elevated in active SLE with pulmonary infections. Serum MMP-3 in combination with CRP may assist in differentiating from SLE pulmonary infections.


Assuntos
Artrite , Lúpus Eritematoso Sistêmico , Metaloproteinase 3 da Matriz/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Humanos
2.
Eur Cytokine Netw ; 30(2): 67-73, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486401

RESUMO

OBJECTIVE: To detect the effect of interleukin (IL)-34 on the secretion of Receptor activator of nuclear factor kappa-B ligand (RANKL)/Osteoprotegerin (OPG) and Matrix metalloproteinase (MMP)-3 by fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and to investigate whether the effect is mediated by IL-17. METHOD: RA-FLS and RA-PBMCs were stimulated with recombinant human (rh) IL-34, with or without the IL-17 inhibitor Plumbagin. The supernatant of the culture medium was collected and the levels of RANKL, OPG, and MMP-3 were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: RhIL-34 promoted RANKL secretion and inhibited OPG secretion in RA-FLS. The effect was weakened by the addition of the IL-17 inhibitor. In contrast, rhIL-34 had no significant effect on MMP-3 secretion by FLS. RhIL-34 elevated the secretion of RANKL by RA-PBMCs but not by healthy-PBMCs. Furthermore, the secretion of RANKL by RA-PBMCs reduced after the addition of the IL-17 inhibitor. OPG secretion by both RA-FLS and FLS from healthy controls was inhibited by rhIL-34, but were elevated after the addition of the IL-17 inhibitor. RhIL-34 had no significant effect on MMP-3 secretion by both RA-PBMCs and healthy-PBMCs. CONCLUSION: IL-34 enhances RANKL/OPG expression by RA-FLS and RA-PBMCs, and this effect is, indirectly, mediated by IL-17. This cytokine is therefore likely to to play an important role in local joint destruction and systemic osteoporosis in RA, and is therefore a potential therapeutic target for the treatment of this disease.


Assuntos
Artrite Reumatoide/metabolismo , Fibroblastos/metabolismo , Interleucinas/farmacologia , Leucócitos Mononucleares/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Sinoviócitos/metabolismo , Artrite Reumatoide/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Sinoviócitos/efeitos dos fármacos
3.
Invest Ophthalmol Vis Sci ; 60(12): 3776-3785, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31503282

RESUMO

Purpose: To investigate the therapeutic effects of targeting signal transducer and activator of transcription-3 (STAT3) activation on the ocular surface damage of dry eye in mice. Methods: Adult Balb/C and C57BL/6 mice with benzalkonium chloride (BAC) treatment, lacrimal gland excision, and meibomian gland dysfunction were used as dry eye models. The levels of phosphorylated STAT3 (p-STAT3) were detected with immunofluorescence staining and Western blotting. STAT3 inhibition was performed by topical application of STAT3 inhibitor S3I-201. Corneal epithelial barrier function, tear production, and conjunctival goblet cell density were quantified with fluorescein sodium staining, phenol red cotton test, and histochemical staining. The expressions of matrix metalloproteinase (MMP)-3/9, TUNEL, and inflammation cytokines were assessed with immunofluorescence staining, qPCR, and ELISA assays. The therapeutic effect of S3I-201 was further compared with the Janus kinase inhibitor tofacitinib and ruxolitinib. Results: Elevated levels of nuclear p-STAT3 were detected in the corneal and conjunctival epithelium of three dry eye models. Topical application of S3I-201 improved corneal epithelial barrier function, increased tear production and conjunctival goblet cell density in BAC-induced dry eye mice. Moreover, S3I-201 decreased the expression of MMP-3/9, suppressed the apoptosis of corneal and conjunctival epithelial cells, and reduced the levels of IL-1ß, IL-6, IL-17A, and IFN-γ. Compared with tofacitinib and ruxolitinib, the STAT3 inhibitor S3I-201 showed superior improvement of tear production and inflammatory cytokine expression in lacrimal gland. Conclusions: Elevated STAT3 activation is involved in the pathogenesis of dry eye, while targeting STAT3 effectively alleviates BAC-induced ocular surface damage.


Assuntos
Modelos Animais de Doenças , Síndromes do Olho Seco/tratamento farmacológico , Proteínas Inibidoras de STAT Ativados/uso terapêutico , Fator de Transcrição STAT3/antagonistas & inibidores , Administração Oftálmica , Animais , Western Blotting , Túnica Conjuntiva/metabolismo , Citocinas/metabolismo , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Ensaio de Imunoadsorção Enzimática , Epitélio/metabolismo , Epitélio Anterior/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Células Caliciformes/patologia , Marcação In Situ das Extremidades Cortadas , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Soluções Oftálmicas , Fosforilação , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT3/metabolismo , Lágrimas/fisiologia
4.
Dis Markers ; 2019: 9796735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396295

RESUMO

Introduction: Matrix metalloproteinase (MMP) is an emerging disease marker in rheumatic diseases. This is a meta-analysis aimed at systematically reviewing association between serum MMP-3 levels and systematic lupus erythematosus (SLE) activity, which sought to raise interest in MMP-3 as a putative biomarker. Methods: We conducted a meta-analysis of serum MMP-3 levels in patients with SLE and controls. We performed a PubMed search, EMBASE search, and forward search of the retrieved articles published until Oct. 1, 2018. In addition to this, we included data from a case-control study on a national pediatric SLE cohort, in which serum MMP-3 levels were measured in 11 SLE patients and 9 controls (unpublished). Subgroup analyses based on gender and disease activity were performed. Results: A total of 662 cases and 771 controls including 651 patients and 762 controls from 11 publications were studied. We observed significantly higher MMP-3 levels in SLE patients compared to healthy controls (P < 0.001, Hedges' g: 2.104, 95% CI 1.426-2.782). In subgroup analyses, we found a significant elevation of MMP-3 in the patients with nephritis compared to those without (P = 0.006, Hedges' g: 0.611, 95% CI 0.611-1.704). This finding was consistent between patients with persistent proteinuria and those without (P = 0.023, Hedges' g: 1.535, 95% CI 0.207-2.862). Meta-analysis showed no association between MMP-3 levels and gender or anti-double strand DNA antibody titer. Conclusions: Our meta-analysis demonstrated significantly higher MMP-3 levels in SLE patients than in controls and in patients with renal involvement than in those without.


Assuntos
Biomarcadores/metabolismo , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/enzimologia , Metaloproteinase 3 da Matriz/metabolismo , Estudos de Casos e Controles , Humanos , Prognóstico
5.
Gastroenterology ; 157(6): 1572-1583.e8, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31470007

RESUMO

BACKGROUND & AIMS: Transgenic mice (HBUS) that express the epidermal growth factor receptor (EGFR) ligand HBEGF (heparin-binding epidermal growth factor-like growth factor) and a constitutively active G protein-coupled receptor (US28) in intestinal epithelial cells develop serrated polyps in the cecum. Development of serrated polyps depends on the composition of the gut microbiota and is associated with bacterial invasion of the lamina propria, accompanied by induction of inflammation and up-regulation of interleukin 1 beta (IL1B) and matrix metalloproteinase (MMP) 3 in the cecum. We investigated the mechanisms by which these changes contribute to development of serrated polyps. METHODS: We performed studies with C57BL/6 (control) and HBUS mice. To accelerate polyp development, we increased the exposure of the bacteria to the lamina propria by injecting HBUS mice with diphtheria toxin, which binds transgenic HBEGF expressed by the epithelial cells and causes apoptosis. Mice were given injections of IL1B-neutralizing antibody and the MMP inhibitor N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid. Intestinal tissues were collected from mice and analyzed by histology, reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and flow cytometry. We examined fibroblast subsets in polyps using single-cell RNA sequencing. RESULTS: Administration of diphtheria toxin to HBUS mice accelerated development of serrated polyps (95% of treated mice developed polyps before 100 days of age, compared with 53% given vehicle). IL1B stimulated subsets of platelet-derived growth factor receptor alpha+ (PDGRFA+) fibroblasts isolated from cecum, resulting in increased expression of MMP3. Neutralizing antibodies against IL1B or administration of the MMP inhibitor reduced the number of serrated polyps that formed in the HBUS mice. Single-cell RNA sequencing analysis showed subsets of fibroblasts in serrated polyps that express genes that regulate matrix fibroblasts and inflammation. CONCLUSIONS: In studies of mice, we found that barrier breakdown and expression of inflammatory factors contribute to development of serrated polyps. Subsets of cecal PDGFRA+ fibroblasts are activated by release of IL1B from myeloid cells during the early stages of serrated polyp development. MMP3 produced by PDGFRA+ fibroblasts is important for serrated polyp development. Our findings confirm the functions of previously identified serrated polyp-associated molecules and indicate roles for immune and stromal cells in serrated polyp development.


Assuntos
Pólipos do Colo/imunologia , Receptores ErbB/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/patologia , Metaloproteinase 3 da Matriz/metabolismo , Animais , Apoptose/imunologia , Ceco/citologia , Ceco/imunologia , Ceco/patologia , Toxina Diftérica/administração & dosagem , Toxina Diftérica/imunologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/patologia , Receptores ErbB/antagonistas & inibidores , Fibroblastos/imunologia , Fibroblastos/metabolismo , Gefitinibe/farmacologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Interleucina-1beta/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Metaloproteinase 3 da Matriz/imunologia , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos , Camundongos Transgênicos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Sulfonamidas/farmacologia
6.
Arch Oral Biol ; 108: 104530, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31470141

RESUMO

OBJECTIVE: Periodontitis is an inflammatory disease of the supporting tissue around teeth commonly caused by gram-negative bacterial infections. Interleukin (IL)-1ß, a cytokine involved in host immune and inflammatory responses, is known to induce the activation of various intracellular signaling pathways. One of these signaling mechanisms involves the regulation of gene expression by activation of transcription factors (AP-1 and NF-κB). These transcription factors are controlled by mitogen-activated protein kinases (MAPKs), which increase cytokine and matrix metalloproteinase (MMP) expression. We examined the preventive effects of reversine, a 2,6-disubstituted purine derivative, on cytokine and MMP-3 expression in human gingival fibroblasts (HGFs) stimulated with IL-lß. STUDY DESIGN: Western blot analyses were performed to verify the activities of MAPK, p65, p50, and c-Jun and the expression of MMPs in IL-1ß-stimulated HGFs. Cytokine and MMP-3 expression in IL-1ß-stimulated HGFs was measured by real-time quantitative polymerase chain reaction. RESULTS: Reversine decreased the IL-1ß-induced expression of proinflammatory cytokines (IL-6 and IL-8) and MMP-3 in HGFs. Furthermore, the mechanism underlying the effects of reversine involved the suppression of IL-1ß-stimulated MAPK activation and AP-1 activation. CONCLUSION: Reversine inhibits IL-1ß-induced MMP and cytokine expression via inhibition of MAPK/AP-1 activation and ROS generation. Therefore, we suggest that reversine may be an effective therapeutic candidate for preventing periodontitis.


Assuntos
Gengiva/metabolismo , Interleucina-6 , Interleucina-8/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Morfolinas , Purinas , Fibroblastos/metabolismo , Humanos , Interleucina-1beta , Interleucina-6/metabolismo , MAP Quinase Quinase 4/metabolismo , Morfolinas/farmacologia , NF-kappa B , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Purinas/farmacologia , Espécies Reativas de Oxigênio , Fator de Transcrição AP-1
7.
Artif Cells Nanomed Biotechnol ; 47(1): 3259-3264, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31368822

RESUMO

Impairment of type II collagen caused by MMPs in response to overproduction of IL-1ß is an important step in the pathological progression of osteoarthritis (OA). Lunasin, a well-known peptide present in the soybean, has displayed a positive impact on numerous physiological functions. Little information in the effects of lunasin on cartilage degradation has been sought in clinical research before. Here, we report that lunasin suppressed the increase in MMP-3 and MMP-13 caused by IL-1ß. In addition, we found that lunasin could prevent the decrease in TIMP-1 and TIMP-2 expressions caused by IL-1ß. Notably, lunasin suppressed reduction of type II collagen, the basis for articular cartilage. Lunasin also attenuated activation of the JAK2/STAT1/IRF-1 pathway. These effects of lunasin suggest that it might become a promising therapeutic agent for chondro-protective therapy.


Assuntos
Colágeno Tipo II/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Proteínas de Plantas/farmacologia , Cartilagem Articular/citologia , Proliferação de Células/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Humanos , Interleucina-1beta/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Arch Oral Biol ; 107: 104495, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377584

RESUMO

OBJECTIVE: Cyclic tensile force (CTF) modulates physiological responses of periodontal ligament (PDL) cells. PDL cells are mechanosensitive and are able to maintain tissue homeostasis; a process mediated by the expression of particular cytokines including interleukin 6 (IL6). It is unknown whether CTF-induced IL6 regulates the expression of MMPs, enzymes needed for tissue remodeling. DESIGN: Human PDL cells were subjected to 10% elongation strain of CTF at a frequency of 60 rpm continuously for 6 h. RNA and proteins were extracted and analyzed for IL6 and MMP expression by quantitative real-time PCR and ELISA, respectively. Using a neutralizing anti-IL6 antibody and addition of recombinant human IL6 at concentrations of 0.1, 1, 10 ng.mL-1 were performed to clarify whether CTF-upregulated IL6 increased MMP expression. Inhibitors of intracellular signaling molecules were employed to reveal possible pathway(s) of IL6-induced MMP expression. RESULTS: CTF-induced IL6 expression coincided with an increased MMP3 expression. A neutralizing anti-IL6 antibody attenuated the CTF-increased MMP3 expression, whereas stimulating the cells with recombinant human IL6 increased MMP3 expression. Both PI3K and MAPK pathways were essential in the IL6 induced expression of MMP3. CONCLUSION: Our findings suggest a role of CTF in the modulation of expression of IL6 and MMP3 and thus in the regulation of homeostasis and remodeling of the periodontal ligament.


Assuntos
Interleucina-6/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Ligamento Periodontal/citologia , Estresse Mecânico , Células Cultivadas , Humanos , Transdução de Sinais , Regulação para Cima
9.
Toxicol Lett ; 314: 18-26, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299270

RESUMO

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFß) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFß signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFß signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention.


Assuntos
Articulações/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Osteoartrite/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fatores Etários , Agrecanas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Condrogênese/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Feminino , Idade Gestacional , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulações/metabolismo , Articulações/patologia , Masculino , Exposição Materna , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Gravidez , Ratos Wistar , Fatores de Risco , Fatores Sexuais
10.
Mol Med Rep ; 20(2): 915-930, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173206

RESUMO

Osteosarcoma is the most common type of malignant bone cancer, which often affects teenagers and young adults. The present study aimed to screen for critical genes and microRNAs (miRNAs/miRs) involved in osteosarcoma. A total of four microarray datasets (accession numbers GSE32981, GSE21257, GSE14827 and GSE14359) were downloaded from the Gene Expression Omnibus database. Following data preprocessing, module analysis was performed to identify the stable modules using the weighted gene co­expression network analysis (WGCNA) package. The differentially expressed genes (DEGs) between metastatic samples and non­metastatic samples were screened, followed by gene co­expression network construction, and Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Subsequently, prognosis­associated genes were screened and a miRNA­target gene regulatory network was constructed. Finally, the data for critical genes were validated. WGCNA analysis identified six modules; blue and yellow modules were significantly positively associated with osteosarcoma metastasis. A total of 1,613 DEGs were screened between primary tissue samples and metastatic samples. Following comparison of the genes in the two (blue and yellow) modules, a total of 166 DEGs were identified (metastatic samples vs. non­metastatic samples). Functional enrichment analysis demonstrated that these DEGs were mainly involved in 'defense response', 'p53 signaling pathway' and 'lysosome'. By utilizing the clinical information in GSE21257, 10 critical genes associated with osteosarcoma prognosis were obtained, including CTP synthase 2 (CTPS2), tumor protein p53 inducible protein 3 (TP53I3) and solute carrier family 1 member 1 (SLC1A1). In addition, hsa­miR­422a and hsa­miR­194 were highlighted in the miRNA­target gene network. Finally, matrix metallopeptidase 3 (MMP3) and vascular endothelial growth factor B (VEGFB) were predicted as critical genes in osteosarcoma metastasis. CTPS2, TP53I3 and SLC1A1 may serve major roles in osteosarcoma development, and hsa­miR­422a, hsa­miR­194, MMP3 and VEGFB may be associated with osteosarcoma metastasis.


Assuntos
Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Neoplasias/genética , Osteossarcoma/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Carbono-Nitrogênio Ligases/genética , Carbono-Nitrogênio Ligases/metabolismo , Bases de Dados Genéticas , Transportador 3 de Aminoácido Excitatório/genética , Transportador 3 de Aminoácido Excitatório/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Mapeamento de Interação de Proteínas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Análise de Sobrevida , Fator B de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/metabolismo
11.
Artif Cells Nanomed Biotechnol ; 47(1): 2139-2145, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31146598

RESUMO

Osteoarthritis (OA) is a common joint disease for which a safe and reliable treatment has yet to be developed. Here, we demonstrated the potential benefit of treatment with paeonol, a derivative of Paeonia suffruticosa, in the treatment and prevention of OA. Chondrogenic cell line ATDC5 cells were cultured with IL-1ß and the effects of paeonol were assessed through qRT-PCR, western blot analysis, MTT, ELISA, and NF-κB luciferase reporter gene assay. Our findings demonstrate a novel ability of paeonol to inhibit numerous factors of OA, including expressions of IL-6, TNF-α, NOX2, PTGS2, NUCB2/nesfatin-1, ICAM-1, VCAM-1, MMP-3/13, degradation of type II collagen, and NF-κB activation through the rescue of IκBα. Additionally, we assessed the effects of paeonol on cell viability to confirm its safety. These findings implicate a valuable potential role of paeonol in the treatment and prevention of OA.


Assuntos
Acetofenonas/farmacologia , Condrócitos/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Interleucina-1beta/farmacologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Proteólise/efeitos dos fármacos , Acetofenonas/uso terapêutico , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , NADPH Oxidase 2/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Osteoartrite/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismo
12.
Appl Biochem Biotechnol ; 189(3): 729-744, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31111375

RESUMO

Vina-ginsenoside R7 (R7) has been exhibited to engage in multiple pharmacological activities, such as antioxidant and anti-inflammatory activities. However, no photoaging-related studies have been performed on R7. Research is being conducted with the aim of assessing whether treatment with R7 has a protective effect on UVB-induced photoaging skin. Our results show that UVB exposure directly reduces matrix metalloproteinase (MMP) secretion through R7 by restraining the AP-1/MAPK pathway and blocks extracellular matrix (ECM) expression degradation. In addition, R7 improves the expression of transforming growth factor beta 1 (TGF-ß1), and type I procollagen also facilitates the synthesis of collagen by the TGF-ß/Smad signal transduction pathway. Finally, R7 valid blocks nuclear factor-κB (NF-κB) activation and enhances antioxidative stress capacity through activated nuclear factor (erythroid derived 2)-like 2 (Nrf2). In particular, the application of R7 restrains pro-inflammatory cytokines (TNF-α, IL-6, iNOS), which trigger ECM, degrade enzyme production, and suppress vascular endothelial growth factor (VEGF) secretion. In conclusion, R7 may constitute a promising cosmetic ingredient that can protect against skin photodamage resulting from detrimental UVB irradiation.


Assuntos
Anti-Inflamatórios/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Ginsenosídeos/farmacologia , Proteínas Luminescentes/farmacologia , Pele/citologia , Raios Ultravioleta/efeitos adversos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Colágeno Tipo I/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos da radiação , Humanos , Interleucina-6/metabolismo , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteólise/efeitos dos fármacos , Proteólise/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese
13.
J Med Food ; 22(10): 1032-1040, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31120380

RESUMO

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease resulting in joint destruction and disability in the adult population. The etiology of RA is not well understood and presently there is no known cure for this disease. The accumulation and proliferation of fibroblast-like synoviocytes may be involved in cartilage destruction. Both in vitro and in vivo studies support an anti-inflammatory role of dietary polyphenols, the bioactive constituents found in fruits and vegetables. The objective of this study was to investigate the anti-inflammatory role of blueberry polyphenols (BBPs) using rabbit synoviocytes stimulated with tumor necrosis factor alpha (TNFα). Rabbit synoviocytes (HIG-82) were treated with varying doses of BBPs and stimulated with TNFα. Stimulation of rabbit synoviocytes with the proinflammatory cytokine TNFα increased cell proliferation by ∼19% compared with the nonstimulated control. Cell proliferation was significantly decreased in a dose-dependent manner by the treatment with BBPs. Post-TNFα stimulation, cells treated with BBPs resulted in decreases in interleukin 1 beta and nuclear factor kappa B (NFκB) concentration. Reverse transcription-polymerase chain reaction analysis showed that matrix metalloproteinase 3 increased fivefold in the control TNFα-stimulated group, but was decreased by threefold in the blueberry treatment group. These results suggest that downregulation of proinflammatory cytokines and transcription factor NFκB by naturally occurring bioactives such as BBPs may be a potential therapeutic strategy for reducing inflammation associated with RA.


Assuntos
Anti-Inflamatórios/farmacologia , Mirtilos Azuis (Planta)/química , Polifenóis/farmacologia , Sinoviócitos/efeitos dos fármacos , Animais , Artrite Reumatoide , Proliferação de Células , Células Cultivadas , Frutas/química , Interleucina-1beta/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , NF-kappa B/metabolismo , Compostos Fitoquímicos/farmacologia , Coelhos , Fator de Necrose Tumoral alfa/farmacologia
14.
Med Sci Monit ; 25: 3815-3824, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31116709

RESUMO

BACKGROUND Pelvic organ prolapse (POP) is due to age-related atrophy and the weakening of the tissues of the pelvic floor, with degradation of collagen and extracellular matrix (ECM) by metalloproteinases (MMPs). This study aimed to investigates the role of the age-related enzyme klotho, encoded by the KL gene, in cultured fibroblasts obtained from patients with POP and the levels of reactive oxygen species (ROS), interleukin-6 (IL-6), and MMPs. MATERIAL AND METHODS Pelvic floor fibroblasts were obtained from connective tissue from three patients with POP and three normal subjects. Cell proliferation and ROS production were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry. Levels of interleukin-6 (IL-6), klotho, metalloproteinase-1 (MMP-1), MMP-3, extracellular signal-regulated kinases 1/2 (ERK1/2), and p-ERK1/2 were measured by enzyme-linked immunoassay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. RESULTS In cultured pelvic floor fibroblasts from patients with POP, the expression of klotho protein and klotho mRNA were significantly down-regulated in fibroblasts from patients with POP compared with normal fibroblasts. Klotho supplementation in cultured fibroblasts for patients with POP included increased cell growth, reduced expression of ROS reduction, and reduced the secretion of IL-6. Using qRT-PCR and Western blot, klotho supplementation of fibroblasts from patients with POP increased cell growth and reduced the levels of IL-6 and ROS in a dose-dependent way. CONCLUSIONS Klotho protein reduced the expression of MMP-1 and MMP-3 in fibroblasts from patients with POP by down-regulating the phosphorylation of ERK1/2.


Assuntos
Glucuronidase/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Prolapso de Órgão Pélvico/metabolismo , Adulto , Idoso , Células Cultivadas , China , Colágeno/metabolismo , Regulação para Baixo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Glucuronidase/genética , Humanos , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Pessoa de Meia-Idade , Diafragma da Pelve , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
15.
Int Immunopharmacol ; 73: 370-378, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132732

RESUMO

Our study aimed to determine the effects of sodium tanshinone IIA sulfonate (STS) on proliferation, migration, invasion, and inflammation in rheumatoid arthritis human fibroblast-like synoviocytes (RA-HFLSs). Firstly, results demonstrated STS reduced proliferation, migration, invasion in HFLSs. Also, we found that STS could alleviate the reorganizations of F-actin cytoskeleton in TNF-α-treated HFLSs. In addition, STS decreased the production of IL-1ß, IL-6, MMP-1, and MMP-3 in TNF-α-treated RA-HFLSs. Further study showed that STS blocked MAPK/NF-κB activations in TNF-α-stimulated RA-HFLSs. Moreover, we illustrated that STS could alleviate rheumatoid arthritis progression and prevent inflammation damage in joint tissues of collagen-induced arthritis (CIA) mice. Taken together, this study suggested that STS inhibited proliferation, migration, invasion, and inflammation of RA-HFLSs by blocking MAPK/NF-κB pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Fenantrenos/farmacologia , Sinoviócitos/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Camundongos Endogâmicos DBA , Fenantrenos/uso terapêutico , Sinoviócitos/fisiologia , Fator de Necrose Tumoral alfa/farmacologia
16.
Drug Dev Res ; 80(5): 637-645, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31032997

RESUMO

Osteoarthritis (OA) is one of the most chronic degenerative arthritic diseases, which gradually results in chondrocyte changes, articular cartilage degeneration, subchondral bone sclerosis, joint pain, swelling, and dysfunction. Berberine (BBR) has various confirmed biological activities, such as anti-inflammatory and antioxidant activities. However, the effect of BBR on the production of inflammation-associated proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, metalloproteinases (MMPs), Collagen II, TNF-α, and IL-6 via the MAPK (mitogen-activated protein kinases) pathway in IL-1ß-stimulated rat chondrocytes, has not yet been studied. Thus, the purpose of this study was to evaluate whether BBR would decrease the production of inflammation-associated proteins through the MAPK signal pathway. Rat chondrocytes were cultured and pretreated with BBR at different concentrations (0, 25, 50, and 100 µM) and then stimulated with or without IL-1ß (10 ng/mL). The mRNA expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 was measured by real-time polymerase chain reaction (RT-PCR), and the protein expression of iNOS, COX-2, Collagen II, MMP-3,MMP-13, and MAPKs were measured by Western blotting. The results showed that the expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 increased in the IL-1ß-treated group and BBR showed an ability to inhibit the elevated expression under the pretreatment. Furthermore, the IL-1ß-induced downregulation of Collagen II could be ameliorated by BBR. Moreover, the expression of MAPKs was significantly decreased by BBR. These results demonstrated that BBR had the anti-catabolic and anti-inflammation abilities that were through the MAPKs in IL-1ß-induced rat chondrocytes. These findings may provide a novel therapeutic choice for treatment of OA using BBR.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Condrócitos/citologia , Interleucina-1beta/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Mol Biol Rep ; 46(3): 2631-2641, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989556

RESUMO

The prevalence of atherosclerosis has increased significantly in the recent years due to sedentary lifestyle and high-fat diet. However, the association between saturated fat intake and the increased risk for atherosclerotic cardiovascular diseases remains heavily debated. Lauric acid belongs to the saturated fatty acid group and its unique medium chain fatty acid properties are proven to be beneficial to humans in many ways. Thus, the aim of this project is to investigate the effect of lauric acid on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes-ADAMTS-1, ADAMTS-4, and ADAMTS-5-in macrophages. These genes encode for proteases that participate in the extracellular matrix remodeling and they play important roles in the vulnerability of atherosclerotic plaque. Here, we show that the treatment of 20 µM of lauric acid successfully reduced both transcriptional and translational expressions of these genes in THP-1 differentiated macrophages after 24-h incubation. Further cell signaling experiments using a panel of kinase inhibitors and phosphorylated antibodies proved that lauric acid down-regulated ADAMTS-1 by reducing the activation of PI3K and JNK at Tyr458 and Tyr185, respectively. Finally, JNK1 siRNA knockdown assay confirmed that ADAMTS-1 was regulated through JNK pathway, and lauric acid interfered with this pathway to down-regulate ADAMTS-1 expression. Although preliminary, this present study indicates that lauric acid has the potential to stabilize atherosclerotic plaque and may prevent thrombosis by interfering with the ADAMTS-1 expression through PI3K/JNK pathways.


Assuntos
Proteína ADAMTS1/metabolismo , Aterosclerose/metabolismo , Ácidos Láuricos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Proteína ADAMTS1/biossíntese , Proteína ADAMTS1/genética , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica , Humanos , Macrófagos/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Metaloendopeptidases/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Células THP-1
18.
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
19.
Artif Cells Nanomed Biotechnol ; 47(1): 1628-1634, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31010320

RESUMO

Chronic inflammation in fibroblast-like synoviocytes (FLSs) induced by pro-inflammatory cytokines such as TNF-α plays a key role in the pathogenesis of rheumatoid arthritis (RA). The neurokinin-1 receptor (NK-1R) is one of the G protein-coupled receptors (GPCRs) mediating the intracellular signalling of substance P (SP). However, the possible implications of NK-1R in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and the pathogenesis of RA have not yet been reported. In the current study, we report that NK-1R is expressed in FLSs. Importantly, NK-1R expression was found to be significantly increased in RA-FLSs compared to normal FLSs. Interestingly, we found that treatment with tumour necrosis factor (TNF)-α increased the expression of NK-1R at both the gene and protein levels. Treatment with the NK-1R antagonist aprepitant reduced TNF-α-induced expression of NADPH oxidase 4 (NOX-4) and generation of reactive oxygen species (ROS) in FLSs. Our results also display that blockage of NF-1R using aprepitant inhibited TNF-α-induced expression and secretion of proinflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, and IL-8. Consistently, aprepitant prevented TNF-α-induced expression of matrix metalloproteinases (MMPs), including matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13). Mechanistically, our data demonstrate that treatment with aprepitant inhibited TNF-α-induced phosphorylation and degradation of inhibitor of NF-κB (IκBα). Notably, aprepitant attenuated TNF-α-induced nuclear translocation of nuclear factor κB (NF-κB) p65 and reduced luciferase activity of NF-κB in FLSs. The findings implicated a novel function of NK-1R in RA-FLSs. Blockage of NK-1R using its specific antagonist aprepitant might provide a new therapeutic strategy for RA.


Assuntos
Aprepitanto/farmacologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Fibroblastos/patologia , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Receptores da Neurocinina-1/metabolismo , Sinoviócitos/efeitos dos fármacos , Aprepitanto/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Antagonistas do Receptor de Neuroquinina-1/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Receptores da Neurocinina-1/genética , Transdução de Sinais/efeitos dos fármacos , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Fator de Necrose Tumoral alfa/metabolismo
20.
Theriogenology ; 131: 123-132, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959438

RESUMO

This study was designed to examine changes in target transcript abundance in endometrial explants exposed to pregnancy-associated glycoproteins (PAGs). Endometrial explants from pregnant and non-pregnant heifers collected on day18 (day 0: day of insemination) were incubated in the absence or presence of PAGs (15 µg/ml). The PAGs represented a mixture comprised of approximately equal amounts of bovine PAGs 4, 6, and 9. Samples were harvested for RNA extraction after 24 h or 96 h of incubation. Transcript abundance for target genes related to prostaglandin synthesis (PTGES), a chemokine (CXCL5) and tissue remodeling (EMMPRIN; MMPs 1, 2, 3, 7, 8, and 9; PLAU; SPP1; TIMP1 and TIMP2) were analyzed by quantitative PCR. Changes in relative transcript abundance for MMP1, MMP3, MMP7, PLAU, EMMPRIN and SPP1 were observed after PAG exposure in both non-pregnant and pregnant endometrium (P < 0.05). However, some of the transcripts associated with tissue remodeling were altered only at certain time points (either 24 h or 96 h). The transcript for bovine CXCL5 was increased in non-pregnant endometrium four- and six-fold at 24 h and 96 h of PAG exposure, respectively (P < 0.05); in pregnant endometrium, only the 24 h incubation period exhibited an elevation in CXCL5 (P < 0.05). In non-pregnant endometrium, both PTGES and MMP9 were elevated after exposure to PAGs for 24 h (P < 0.05) but not in the other samples. Some interferon-responsive transcripts (IFI6, ISG15) were found to be more abundant (P < 0.05) in pregnant endometrium after 96 h exposure to PAGs compared to endometrium that had not been exposed to the PAGs. Likewise, ISG15 message was elevated (P = 0.06) in non-pregnant endometrium after 24 h incubation with PAGs. These results indicate that the PAGs used in this experiment were able to induce changes in endometrial transcripts encoding for proteins associated with matrix remodeling as well as chemokine production and prostaglandin release.


Assuntos
Bovinos , Endométrio/metabolismo , Glicoproteínas/farmacologia , Animais , Basigina/genética , Basigina/metabolismo , Feminino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Osteopontina/genética , Osteopontina/metabolismo , Gravidez , RNA Mensageiro/metabolismo
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