Therefore, this study manifested that miR-423-5p overexpression protected HG-induced podocyte damage by inhibiting ROS generation via targeting Nox4, providing a potential therapeutic strategy against DN.
Finally, electron microscopy revealed that podocytes of glomeruli isolated from <i>Trpc</i>6-knockout or <i>Trpc</i>5/6 double-knockout mice were protected from damage induced by H<sub>2</sub>O<sub>2</sub> to the same extent.<b>Conclusions</b> These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.
Among NADPH oxidase isoforms, NADPH oxidase4 (Nox4) is highly expressed in the kidney and has an important role in kidney diseases, such as diabetic nephropathy and renal carcinoma.
These findings indicated that Nox4 potentially mediates HG‑induced HKC cell apoptosis via the Notch pathway, and may be involved in renal tubular epithelial cell injury in DN.
Take together, this study demonstrated that naringin ameliorates diabetic nephropathy by inhibiting NOX4, contributing to a better understanding of the progression of DN.
Our findings suggest that APX-115 may be as effective or may provide better protection than the dual Nox1/Nox4 inhibitor, and pan-Nox inhibition with APX-115 might be a promising therapy for diabetic nephropathy.
Although much emphasis has been placed on the role of NADPH oxidase 4 in this setting, a growing body of work continues to uncover the key roles for other Nox family members, not only in diabetic kidney disease, but also in a diverse array of renal pathological conditions.
In human podocytes, silencing of the Nox4 gene resulted in reduced production of ROS and downregulation of proinflammatory and profibrotic markers that are implicated in diabetic nephropathy.
The aim of this study was to investigate the role of Nox4 inhibition on TGFβ1-induced fibrotic responses in proximal tubular cells and in a mouse model of diabetic nephropathy.
Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055).