C3AR1 may aggravate diabetic nephropathy by mediating oxidative stress via ITGB2 regulation in renal tubular epithelial cells.

Abstract

Diabetes nephropathy (DN) is the most common chronic complication of diabetes and has become an important cause of end-stage renal failure. Oxidative stress and inflammatory response play important driving roles in the occurrence and development of diabetic nephropathy. As a key gene of DN, C3AR1 has been shown to mediate oxidative stress and inflammation. However, its potential mechanism in DN is still unclear. Here, we found that C3AR1 was upregulated in high glucose (HG)-treated human renal tubular epithelial cells (HK-2) and kidney tissues of DN rats. Interference with C3AR1 protected HK-2 cells from HG-mediated oxidative stress injury. Co-Immunoprecipitation (Co-IP) analysis showed that C3AR1 interacted with ITGB2 and promoted the expression of ITGB2. Overexpression of ITGB2 reversed the inhibition of C3AR1 interference on oxidative stress, apoptosis, and inflammatory response in HG-treated HK-2 cells. The rat DN model was established by unilateral nephrectomy and one-time intraperitoneal injection of 60 mg/kg streptozotocin (STZ), followed by the tail vein injection of the C3AR1 lentivirus interference plasmid. The results showed that interfering with C3AR1 reduced the level of inflammatory markers in the serum and weakened the oxidative stress and pathological damage of kidney tissues in DN rats. This study showed that C3AR1 may contribute to DN by upregulating ITGB2 protein levels to mediate oxidative stress.