title: 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.
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, No. 168, Changhai Road, Yangpu District, Shanghai 200433, China. sandytuteng@sina.com.
authors.forename: Jian-Xia
authors.initials: JX
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, No. 168, Changhai Road, Yangpu District, Shanghai 200433, China. sandytuteng@sina.com.
authors.forename: Qi-Jin
authors.initials: QJ
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, No. 168, Changhai Road, Yangpu District, Shanghai 200433, China. sandytuteng@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Changhai Hospital, The Second Military Medical University, No. 168, Changhai Road, Yangpu District, Shanghai 200433, China. sandytuteng@sina.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000235:genetics*; D015870:Gene Expression; D020868:Gene Silencing; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D018836:Inflammation Mediators; D020782:Matrix Metalloproteinases; D051379:Mice; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D043222:Ubiquitin Thiolesterase; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; D010450:Endopeptidases; C584444:USP22 protein, mouse; D043222:Ubiquitin Thiolesterase; D020782:Matrix Metalloproteinases; D005947:Glucose; D000077185:Resveratrol