Interference of periostin attenuates pathological changes, proinflammatory markers and renal fibrosis in diabetic kidney injury.

Abstract

Diabetic nephropathy (DN) is a prevalent complication of diabetes, in which inflammation and fibrosis are the significant pathogenesis. Periostin is a matricellular protein that functions on stabilizing the extracellular matrix by binding to integrins during development. This study aimed to explored the role of periostin in DN. The animal and cell models of DN were constructed in streptozocin (STZ)-induced mice and high glucose-challenged human mesangial cells (HMCs). The role of periostin in pathological changes, inflammation and fibrosis in DN was investigated through biochemical detection, HE and Masson staining and scores, western blot, enzyme‑linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) assays. Knockdown of periostin counteracted the STZ-induced the ratio of kidney weight and body weight, and the concentrations of urine albumin excretion (UAE), serum creatinine (Scr), urine albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) in mice. Moreover, silencing of periostin alleviated the pathological manifestations and reduced the concentrations of IL-6, TNF-α and IL-1β in mice kidney tissues and sera. Also, downregulation of periostin decreased the relative protein expression of fibronectin, collagen IV and α-SMA in kidney tissues. Meanwhile, interference of periostin attenuated the levels of pro-inflammation factors and the expressions of fibrosis markers in HG-induced HMCs. Interference of periostin resisted DN via attenuating the pro-inflammatory cytokines release and renal fibrosis in diabetic kidney injury. Our study establishes a basis for its further study and underlying application in clinical practice in diagnosing and treating diabetic kidney injury or other relevant diseases.