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Mol Biosyst. 2016 Apr 26;12(5):1445-56. doi: 10.1039/c5mb00722d.

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

Author information

1
Department of Endocrinology, Changhai Hospital, The Second Military Medical University, No. 168, Changhai Road, Yangpu District, Shanghai 200433, China. sandytuteng@sina.com.

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.

PMID:
26953552
DOI:
10.1039/c5mb00722d
[Indexed for MEDLINE]

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