Issue 5, 2016

Silencing of USP22 suppresses high glucose-induced apoptosis, ROS production and inflammation in podocytes

Abstract

Ubiquitin-specific protease 22 (USP22) has been reported to mediate various cellular processes, including cell proliferation and apoptosis. However, its role in high glucose-induced podocytes and diabetic rats remains unknown. In the current study, podocytes were treated with different concentrations of D-glucose to establish a high glucose-induced injury model. Additionally, intravenous tail injection of rats with 65 mg kg−1 of streptozotocin (STZ) was performed to establish a diabetic rat model. Our findings showed that the treatment of podocytes with high D-glucose significantly increased the USP22 expression level. Silencing of USP22 in podocytes attenuated high D-glucose-induced apoptosis and inflammatory responses, evidenced by increases in proliferation and MMP levels and decreases in the apoptotic rate, ROS production, the Bax/Bcl-2 ratio, caspase-3 expression and secretion of TNF-α, IL-1β, IL-6 and TGF-β1. In addition, podocytes with USP22 overexpression significantly enhanced the effect of high D-glucose-induced apoptosis and inflammatory responses. Similar to the protective effect of USP22 knockdown, resveratrol (RSV) depressed not only high D-glucose- and USP22 overexpression-induced cytotoxicity, but also the secretion of TNF-α, IL-1β, IL-6 and TGF-β1. Notably, silencing of USP22 in diabetic rats conferred a similar protective effect against high glucose-induced apoptosis and inflammation. Taken together, the findings of the present study have demonstrated for the first time that USP22 inhibition attenuates high glucose-induced podocyte injuries and inflammation.

Graphical abstract: Silencing of USP22 suppresses high glucose-induced apoptosis, ROS production and inflammation in podocytes

Article information

Article type
Paper
Submitted
27 Okt 2015
Accepted
21 Feb 2016
First published
08 Mac 2016

Mol. BioSyst., 2016,12, 1445-1456

Silencing of USP22 suppresses high glucose-induced apoptosis, ROS production and inflammation in podocytes

J. Shi, Q. Wang, H. Li and Q. Huang, Mol. BioSyst., 2016, 12, 1445 DOI: 10.1039/C5MB00722D

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