Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity | Zendy

HengHsiung Wu | Zendy; ChaoJung Chen | Zendy; Peiyu Lin | Zendy; Yu-Huei Liu | Zendy

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Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity

Author(s) -

HengHsiung Wu,

ChaoJung Chen,

Peiyu Lin,

Yu-Huei Liu

Publication year - 2019

Publication title -

journal of food and drug analysis

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.277

H-Index - 54

eISSN - 2224-6614

pISSN - 1021-9498

DOI - 10.1016/j.jfda.2019.09.003

Subject(s) - prohibitin , downregulation and upregulation , podocyte , glomerular basement membrane , chemistry , microbiology and biotechnology , gene knockdown , membranous nephropathy , cancer research , biology , mitochondrion , kidney , glomerulonephritis , biochemistry , proteinuria , endocrinology , apoptosis , gene

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, when not effectively treated. The aim of this study was to discover new targets for the diagnosis and treatment of MN. A reliable mouse model of MN was used by the administration of cationic bovine serum albumin (cBSA). Mice with MN exhibited proteinuria, histopathological changes, and accumulation of immune complexes in the glomerular basement membrane. Label-free proteomics analysis was performed to identify changes in protein expression, and the overexpressed proteins were evaluated. There were 273 proteins that showed significantly different expression in mice with MN, as compared to the controls. String analysis showed that functions related to cellular catabolic processes were downregulated in MN. Among the differentially expressed proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2) were upregulated in the kidneys of mice with MN, as demonstrated by immunohistochemistry (IHC), and this upregulation was observed in both the tubular cells and glomeruli. Both shRNA-mediated knockdown of PHB1 or PHB2 inhibited tumor suppressor p53 expression and significantly promoted podocyte proliferation. In addition, both PHB1 and PHB2 were responsible for cBSA-induced cytotoxicity. Microarray analysis further revealed that the upregulation of PHB1 and PHB2 may be due to a blockage of proteasome activity. These data demonstrate that the upregulation of PHB2 is involved in cBSA-mediated podocyte cytotoxicity, which may lead to MN development.

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