Neuregulin 4 attenuate tubulointerstitial fibrosis and advanced glycosylation end products accumulation in diabetic nephropathy rats via regulating TNF-R1 signaling.

Neuregulin 4 (Nrg4) play important roles in the pathogenesis of obesity-associated disorders, including type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). This study aims to investigate roles of Nrg4 in the pathophysiologic mechanism underlying the progression of tubulointerstitial fibrosis (TIF) in diabetic nephropathy (DN). In present study, Nrg4 is under-expression in serum and renal tissue of diabetic nephropathy rats. In present study, Nrg4 attenuate renal function injury, tubulointerstitial fibrosis, inflammation and suppress the expression levels of advanced glycosylation end products (AGEs) in vivo and vitro. Furthermore, the results reveal that Nrg4 ameliorates fibrosis and attenuate the expression of AGEs and inflammation via TNF-R1 signaling instead of TNF-R2 signaling in HK-2 cells. In conclusion, these results revealed that Nrg4 may effectively ameliorates TIF and attenuate the expression of AGEs in DN through TNF-R1 signaling instead of TNF-R2 signaling. We have provided evidence indicating that Nrg4 possesses therapeutic effect on TIF in DN. AJTR