Dataset Information

Research advance in the mechanism for oxidative stress-induced podocyte injury in diabetic kidney disease.

ABSTRACT: Diabetic kidney disease (DKD) is one of the serious microvascular complications of diabetes mellitus (DM), and it is also the leading cause for the end-stage kidney disease (ESKD), but the clinical treatment for it is limited at present. The pathogenesis of DKD is complex. Many studies have shown that podocyte injury is the core event of DKD, and oxidative stress is closely related to podocyte injury in DKD. Oxidative stress mediates podocyte apoptosis and slit diaphragm damage in DKD through various pathways. The antioxidant drugs can slow down the progression of DKD through reducing podocyte injury and are expected to enter clinical trials. The research status of antioxidant drugs is very important, which will provide new strategies for the clinical treatment of DKD.

SUBMITTER: Ao L

PROVIDER: S-EPMC10930572 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Research advance in the mechanism for oxidative stress-induced podocyte injury in diabetic kidney disease.

Ao Liyun L Xie Yanyun Y

Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 20211201 12

Diabetic kidney disease (DKD) is one of the serious microvascular complications of diabetes mellitus (DM), and it is also the leading cause for the end-stage kidney disease (ESKD), but the clinical treatment for it is limited at present. The pathogenesis of DKD is complex. Many studies have shown that podocyte injury is the core event of DKD, and oxidative stress is closely related to podocyte injury in DKD. Oxidative stress mediates podocyte apoptosis and slit diaphragm damage in DKD through va ...[more]

PMID: 35232911

Similar Datasets

Project description:Diabetic glomerular injury is a major complication of diabetes mellitus and is the leading cause of end stage renal disease (ESRD). Healthy podocytes are essential for glomerular function and health. Injury or loss of these cells results in increased proteinuria and kidney dysfunction and is a common finding in various glomerulopathies. Thus, mechanistic understanding of pathways that protect podocytes from damage are essential for development of future therapeutics. MicroRNA-146a (miR-146a) is a negative regulator of inflammation and is highly expressed in myeloid cells and podocytes. We previously reported that miR-146a levels are significantly reduced in the glomeruli of patients with diabetic nephropathy (DN). Here we report generation of mice with selective deletion of miR-146a in podocytes and use of these mice in models of glomerular injury. Induction of glomerular injury in C57BL/6 wildtype mice (WT) and podocyte-specific miR-146a knockout (Pod-miR146a-/-) animals via administration of low-dose lipopolysaccharide (LPS) or nephrotoxic serum (NTS) resulted in increased proteinuria in the knockout mice, suggesting that podocyte-expressed miR-146a protects these cells, and thus glomeruli, from damage. Furthermore, induction of hyperglycemia using streptozotocin (STZ) also resulted in an accelerated development of glomerulopathy and a rapid increase in proteinuria in the knockout animals, as compared to the WT animals, further confirming the protective role of podocyte-expressed miR-146a. We also confirmed that the direct miR-146a target, ErbB4, was significantly upregulated in the diseased glomeruli and erlotinib, an ErbB4 and EGFR inhibitor, reducedits upregulation and the proteinuria in treated animals. Primary miR146-/- podocytes from these animals also showed a basally upregulated TGFβ-Smad3 signaling in vitro. Taken together, this study shows that podocyte-specific miR-146a is imperative for protecting podocytes from glomerular damage, via modulation of ErbB4/EGFR, TGFβ, and linked downstream signaling.

Dataset Information

Research advance in the mechanism for oxidative stress-induced podocyte injury in diabetic kidney disease.

Publications

Research advance in the mechanism for oxidative stress-induced podocyte injury in diabetic kidney disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets