Brahma-related gene 1 induces apoptosis in a p53-dependent manner in human rheumatoid fibroblast-like synoviocyte MH7A

Abstract

Blocked apoptosis and aggressive inflammatory responses occur in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA) patients. Although Brahma-related gene 1 (BRG1) is considered as a tumor suppressor, few research covers its role in RA. This study aims to reveal effects and potential mechanisms of BRG1 in human FLS cell line MH7A.BRG1 expression in MH7A cells was altered by transfection of overexpression vectors or short hairpin RNAs (shRNAs). Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry after transfection. Factors involved in inflammation and apoptosis were quantified by qPCR and Western blot. The interaction between BRG1 and p53 was assessed by immunoprecipitation (IP).Results showed that BRG1 overexpression significantly suppressed MH7A cell viability and induced apoptosis (P < 0.01), and its knockdown had opposite effects. BRG1 reduced mRNA levels of matrix metallopeptidase 3, TIMP metallopeptidase inhibitor 2, cyclooxygenase 2, and interleukin 6, implying its suppressive effects on inflammation. BRG1 interacted with and promoted p53 (P < 0.05). B-cell chronic lymphocytic leukemia/lymphoma 2 was suppressed (P < 0.05), while cytochrome c, caspase 3 (CASP3) and CASP9 were activated (P < 0.01) by BRG1. However, the regulation on these factors was abrogated by p53 knockdown (P < 0.01).These findings suggest that BRG1 may induce apoptosis and suppress inflammation in MH7A cells. Potential functional mechanisms involve the regulation of apoptotic factors by BRG1, which may depend on the recruitment and promotion of p53. This study provides the essential proof for applying BRG1 to the molecular therapy of RA.

Current Biomarkers of Apoptosis Process in Chronically Inflamed Nasal Sinus Epithelium: Representatives of BAX, Bcl-2 and miRNA Group

“…CRSwNP can be, however, compared to other in ammatory processes. Hou and Xing found increased expression levels of p53, CASP3 and CASP9 and decreased expression levels of Bcl-2 in patients with RA 51 . Our results suggest a similar in ammation pattern.…”

Expression of Apoptosis-Related Biomarkers in Inflamed Nasal Sinus Epithelium of Patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)—Evaluation at mRNA and miRNA Levels

“…CRSwNP can be, however, compared to other inflammatory processes. For example, Hou et al found increased expression levels of P53 , CASP3 , and CASP9 and decreased expression levels of BCL-2 in patients with rheumatoid arthritis (RA) [ 51 ]. Our data corroborate this gene expression pattern and suggest a convergent molecular mechanism of apoptosis activation.…”

Epigenetic Regulation of Immune and Inflammatory Responses in Rheumatoid Arthritis

“…Hou et al. revealed that SMARCA4 induces apoptosis of human rheumatoid fibroblast-like synoviocyte MH7A cells in a p53-dependent pattern ( 48 ). Therefore, consistent with the results of these previous studies, our study confirms the important role of SMARCA4 in the pathogenesis of RA.…”