Loss of epithelial membrane protein 2 aggravates podocyte injury via upregulation of caveolin-1

Xiaoyang Wan, Zhaohong Chen, Won Il Choi, Heon Yung Gee, Friedhelm Hildebrandt, Weibin Zhou

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26 Citations (Scopus)


Nephrotic syndrome is a CKD defined by proteinuria with subsequent hypoalbuminemia, hyperlipidemia, and edema caused by impaired renal glomerular filtration barrier function. We previously identified mutations in epithelial membrane protein 2 (EMP2) as a monogenic cause of this disease. Here, we generated an emp2-knockout zebrafish model using transcription activator-like effector nuclease–based genome editing. We found that loss of emp2 in zebrafish upregulated caveolin-1 (cav1), a major component of caveolae, in embryos and adult mesonephric glomeruli and exacerbated podocyte injury. This phenotype was partially rescued by glucocorticoids. Furthermore, overexpression of cav1 in zebrafish podocytes was sufficient to induce the same phenotype observed in emp2 homozygous mutants, which was also treatable with glucocorticoids. Similarly, knockdown of EMP2 in cultured human podocytes resulted in increased CAV1 expression and decreased podocyte survival in the presence of puromycin aminonucleoside, whereas glucocorticoid treatment ameliorated this phenotype. Taken together, we have established excessive CAV1 as a mediator of the predisposition to podocyte injury because of loss of EMP2, suggesting CAV1 could be a novel therapeutic target in nephrotic syndrome and podocyte injury.

Original languageEnglish
Pages (from-to)1066-1075
Number of pages10
JournalJournal of the American Society of Nephrology
Issue number4
Publication statusPublished - 2016

Bibliographical note

Publisher Copyright:
Copyright © 2016 by the American Society of Nephrology.

All Science Journal Classification (ASJC) codes

  • General Medicine


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