Long non-coding RNA L13Rik promotes high glucose-induced mesangial cell injury by regulating miR-2861/CDKN1B axis

Abstract

AbstractDiabetic nephropathy (DN) is a frequent and severe microvascular complication of diabetes. Glomerular mesangial cell (MC) injury occurs at the initial phase of DN and acts as a critical role in the pathogenesis of DN. Given the importance of long non-coding RNA (lncRNA) in regulating MC hyperplasia and extracellular matrix (ECM) accumulation, it is essential to identify functional lncRNAs during MC injury. Here a novel lncRNA, C920021L13Rik (L13Rik for short), was identified to up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic rats was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik on regulating HG-induced MC injury was assessed using cell counting kit-8 (CCK-8) and western blot assay to analyze MC viability and ECM accumulation. We found that L13Rik level was significantly increased while miR-2861 level was significantly decreased in peripheral blood of DN patients, renal tissues of diabetic rats, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced MC survival, ECM accumulation, and cell hypertrophy. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of its target cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to accelerate MC injury. Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN, and may be a hopeful therapeutic target for DN.