XBP1 inhibits mesangial cell apoptosis in response to oxidative stress via the PTEN/AKT pathway in diabetic nephropathy

Abstract

Diabetic nephropathy ( DN ) is a complication of diabetes mellitus ( DM ) that frequently results in renal disease, and is characterized by a variety of symptoms, including albuminuria. It has been shown that apoptosis of glomerular mesangial cells ( MC s) can aggravate albuminuria and contribute to the development of diabetic glomerulosclerosis. Hence, determination of the mechanisms leading to MC apoptosis may help us gain insights into the pathogenesis of DN . As our understanding of the role of high glucose ( HG ) in MC apoptosis remains elusive, we explored the interplay between X‐box binding protein 1 ( XBP 1) and MC apoptosis in this study. XBP 1 was observed to be downregulated both in vivo and in vitro . Treatment of XBP 1‐overexpressing cells with HG resulted in a decrease of reactive oxygen species ( ROS ) and a suppression of cell apoptosis, concomitant with decreases in cleaved caspase‐3 and Bax. Subsequent analyses demonstrated that XBP 1 overexpression inhibited the expression of phosphatase and tensin homolog deleted on chromosome ten ( PTEN ) and enhanced the activation of AKT in MC s exposed to HG . In addition, XBP 1‐induced injuries in MC were reversed by overexpression of PTEN , and XBP 1 inhibited apoptosis, which was mediated by the activated PTEN / AKT signaling pathway. Thus, our data indicate that XBP 1 can activate the PTEN / AKT signaling pathway, thereby alleviating oxidative stress caused by HG or MC apoptosis. These findings suggest that XBP 1 may have potential in the development of treatment methods for DN .

WITHDRAWN: Dexamethasone reduces podocyte injury through the PTEN-PI3K/Akt signaling pathway

“…DEX treatment could reverse the changes described above; studies have also found that PTEN may be a kind of protective gene in the kidney [23][24][25][26][27] . High expression of PTEN can negatively regulate the PI3K/Akt pathway, inhibit the activation of Akt, improve the phenotype of renal podocytes, and reduce damage to renal podocytes [28] .In early DN, as glomerular damage increases, the expression of PTEN gradually decreases, suggesting that PTEN has a certain correlation with glomerular damage [29][30][31][32] . To con rm the exact mechanism of PTEN in podocyte injury, after silencing the PTEN gene, we found that the expression of the downstream signaling pathway protein AKT increased,podocyte autophagy was signi cantly inhibited, and the expression of the LC3B protein signi cantly decreased.…”

A novel identified circular RNA, circ_0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR‑101b by targeting TGFβRI

“…diabetic nephropathy (dn) is becoming the most pervasive complication for both types i and ii diabetes, and is also the major cause of end-stage renal disease in the majority of developed and developing countries (1). clinically, dn is characterized by mesangial hypertrophy, mesangial cell (Mc) proliferation, albuminuria, extracellular matrix (ecM) accumulation and kidney fibrosis (2,3). It has been recognized that the glomerular Mcs and ecM accumulation are involved in a variety of biological events (4).…”

XCL1 Aggravates Diabetic Nephropathy-Mediated Renal Glomerular Endothelial Cell Apoptosis and Inflammatory Response via Regulating p53/Nuclear Factor-Kappa B Pathway

“…Cell apoptosis is an important aspect of DN pathogenesis [16]. Two vital molecular signaling pathways are involved in cell apoptosis, including the intrinsic pathway and the extrinsic pathway.…”