MicroRNA-27a-3p directly targets FosB to regulate cell proliferation, apoptosis, and inflammation responses in immunoglobulin a nephropathy

• Published in: Biochemical and biophysical research communications 2020-09, Vol.529 (4), p.1124-1130
• Main Authors: Liao, Yu, Wang, Ziyan, Wang, Lixin, Lin, Yanzhao, Ye, Ziyi, Zeng, Xufang, Wei, Fangning
• Format: Article
• Language: English
• Subjects: Apoptosis - genetics; Base Sequence; Cell Line; Cell Proliferation - genetics; Cytokines - metabolism; FosB; Gene Expression Regulation; Glomerulonephritis, IGA - complications; Glomerulonephritis, IGA - genetics; Glomerulonephritis, IGA - pathology; Humans; IgAN; Inflammation - complications; Inflammation - genetics; Inflammation - pathology; Inflammation Mediators - metabolism; Inflammatory cytokine; Kidney function; MicroRNAs - genetics; MicroRNAs - metabolism; MiRNA-27a-3p; Proto-Oncogene Proteins c-fos - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.06.115

Immunoglobulin A nephropathy (IgAN) constitutes the most common primary glomerulonephritis worldwide; however, the exact pathogenesis of IgAN is unknown. Previous genome-wide analysis of microRNA (miRNA) expression in the kidney has confirmed that miRNAs are closely related to the pathological changes of IgAN. Accordingly, in this study we found that miR-27a-3p is upregulated in IgAN kidney tissues in addition to human podocytes and tubule epithelial HK2 but not mesangial cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), flow cytometry, real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays were used to verify the regulatory effects of miR-27a-3p and its inhibition on cell proliferation, apoptosis, and release of inflammatory factors in podocytes and HK2 cells. The target genes of miR-27a-3p were predicted using bioinformatics software; the identity of FosB as a target gene of miR-27a-3p was confirmed by luciferase report assay and western blot. Overall, our findings demonstrated that miR-27a-3p regulates cell apoptosis, cell proliferation, and the release of inflammatory cytokines of human podocytes and HK2 cells by directly targeting FosB. Our results therefore suggested that miR-27a-3p might be associated with the pathophysiology of IgAN and may represent a potential target for further studies related to IgAN mechanism or therapeutics. •Immunoglobulin A nephropathy (IgAN) constitutes a kidney disease that represents one of the most common primary glomerulonephritis disorders worldwide.•Podocyte injury and inflammation is one of the directions to explore the pathogenesis of IgAN.•MiRNAs play an important role in the procession and pathogenesis of IgAN.•MiR-27a-3p regulates podocyte proliferation, apoptosis and the release of inflammatory cytokines by directly target FosB.