Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity
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 (c...
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doaj-7273c3cc3d984ec6970323315e50be7b2020-11-25T02:45:28ZengElsevierJournal of Food and Drug Analysis1021-94982020-01-01281183194Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicityHeng-Hsiung Wu0Chao-Jung Chen1Pei-Yu Lin2Yu-Huei Liu3Graduate Institute of Biomedical Sciences, China Medical University, Taichung, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; Corresponding author. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Fax: +886 4 22033295.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. Keywords: Membranous nephropathy, Prohibitin 1, Prohibitin 2http://www.sciencedirect.com/science/article/pii/S1021949819300870 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heng-Hsiung Wu Chao-Jung Chen Pei-Yu Lin Yu-Huei Liu |
spellingShingle |
Heng-Hsiung Wu Chao-Jung Chen Pei-Yu Lin Yu-Huei Liu Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity Journal of Food and Drug Analysis |
author_facet |
Heng-Hsiung Wu Chao-Jung Chen Pei-Yu Lin Yu-Huei Liu |
author_sort |
Heng-Hsiung Wu |
title |
Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity |
title_short |
Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity |
title_full |
Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity |
title_fullStr |
Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity |
title_full_unstemmed |
Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity |
title_sort |
involvement of prohibitin 1 and prohibitin 2 upregulation in cbsa-induced podocyte cytotoxicity |
publisher |
Elsevier |
series |
Journal of Food and Drug Analysis |
issn |
1021-9498 |
publishDate |
2020-01-01 |
description |
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. Keywords: Membranous nephropathy, Prohibitin 1, Prohibitin 2 |
url |
http://www.sciencedirect.com/science/article/pii/S1021949819300870 |
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