0 240

Cited 15 times in

Loss of Epithelial Membrane Protein 2 Aggravates Podocyte Injury via Upregulation of Caveolin-1.

Authors
 Xiaoyang Wan  ;  Zhaohong Chen  ;  Won-Il Choi  ;  Heon Yung Gee  ;  Friedhelm Hildebrandt  ;  Weibin Zhou 
Citation
 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol.27(4) : 1066-1075, 2016 
Journal Title
 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 
ISSN
 1046-6673 
Issue Date
2016
MeSH
Animals ; Caveolin 1/physiology* ; Humans ; Membrane Glycoproteins/physiology* ; Nephrotic Syndrome/etiology ; Podocytes/physiology* ; Up-Regulation* ; Zebrafish
Keywords
nephrotic syndrome ; podocyte ; proteinuria ; zebrafish
Abstract
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.
Full Text
http://jasn.asnjournals.org/content/27/4/1066
DOI
10.1681/ASN.2014121197
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146525
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse