Suppression of lncRNA Snhg1 inhibits high glucose-induced inflammation and proliferation in mouse mesangial cells. (February 2023)

• Record Type: Journal Article
• Authors: Sheng, Junqin; Lu, Chang; Liao, Zhuojun; Xue, Ming; Zou, Zhouping; Feng, Jianxun; Wu, Bo
• Is Part Of: Toxicology in vitro. Volume 86(2023)
• Publication Date: 2023-02
• Subjects: Diabetic nephropathy -- LncRNA Snhg1 -- Inflammation -- Proliferation -- Mesangial cells; DN diabetic nephropathy -- LncRNA long non-coding RNA -- Snhg1 small nucleolar RNA host gene 1 -- HG high glucose -- MC mesangial cell -- siRNA small interfering RNA -- FISH fluorescence in situ hybridization -- UTR untranslated region; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2022.105482
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Diabetic nephropathy (DN) is the direct cause of end-stage renal disease, and nephritic inflammation plays a role in its growth and advancement. Aberrant expression of long non-coding RNAs (lncRNAs) correlates with many diseases, including DN. In this study, we investigated whether lncRNA small nucleolar RNA host gene 1 (Snhg1) was mechanistically involved in inflammation and mesangial cell (MC) proliferation in DN. We found that Snhg1 was significantly upregulated in DN renal tissues and high glucose (HG)-treated MCs. Overexpression of Snhg1 promoted inflammatory cytokine expression in MCs and MC proliferation under low-glucose conditions; meanwhile, Snhg1 knockdown suppressed inflammatory cytokine production and MC proliferation under HG conditions. Mechanistically, Snhg1 was found to directly bind miR-27b, thereby preventing the miRNA from binding its target KDM6B mRNA. Furthermore, miR-27b overexpression recapitulated the inhibitory effects of Snhg1 knockdown, whereas restoration of Snhg1 expression attenuated the function of miR-27b in MCs under HG conditions. Taken together, these results indicate that suppression of Snhg1 inhibited HG-induced inflammation and proliferation of MCs by regulating the miR-27b/KDM6B axis. Highlights: Levels of Snhg1 were Increased in DN renal tissues and HG-treated MCs. Snhg1 enhances inflammatory cytokine expression and promotes MC proliferation. Snhg1 functions as a miR-27b sponge, consequently regulating KDM6B expression. Snhg1 regulates the inflammatory-cytokine expression and MC proliferation via the miR-27b–KDM6B axis.