Hyperoside Suppresses High Glucose-Evoked Inflammation and Fibrosis in Glomerular Mesangial cells by Downregulating lncRNA RMRP

Objective: Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. Diabetic condition or hyperglycaemia induces profibrotic reactions, which ultimately cause glomerulosclerosis. Hyperoside (HP) possesses diverse biological actions, including cardiovascular, renal, neuroprotective, antifibrotic, and anticancer effects. This study aimed to determine the underlying mechanism of HP on high glucose (HG)-evoked inflammation and fibrosis in glomerular mesangial cells (GMCs). Methods: GMCs were respectively cultured in DMEM medium with 0 or 30 mmol /L D-glucose, termed as negative control (Con) and HG groups. HG group were respectively treated with 4, 8, or 16 nmol/L HP, generating HG+HP-L/-M/-H groups. si-NC or si-lncRNA RMRP -transfected GMCs were treated with 30 mmol /L D-glucose, termed as HG+si-NC, HG+si-lncRNA RMRP. pcDNA or pcDNA-lncRNA RMRP -transfected GMCs were treated with 30 mmol /L D-glucose and 16 nmol/L HP, termed as HG+HP-H+pcDNA, and HG+HP-H+ pcDNA-lncRNA RMRP group. ELISA analyzed IL-6, IL-10 and TNF-α. Western blot detected connective tissue growth factor (CTGF), endothelin-1 (ET-1), and fibronectin (FN) protein levels. RT-qPCR detected lncRNA RMRP levels. Results: HP or lncRNA RMRP silencing decreased IL-6 and TNF-α levels, ET-1, FN and CTGF protein contents, and increased IL-10 levels (P<0.05). HP treatment down-regulated HG-evoked increase of lncRNA RMRP (P<0.05), and lncRNA RMRP up-regulation reversed the inhibition of HP on inflammatory response and fibrosis in GMCSs (P<0.05). HG+HP-H treatment group is the most effective. Conclusion: HP inhibits GMC inflammation and fibrosis induced by HG through down-regulating lncRNA RMRP, providing new insight to the current investigation on therapeutic strategies for DN.