Document Detail


Zona occludens-2 protects against podocyte dysfunction induced by ADR in mice.
MedLine Citation:
PMID:  23034938     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Zona occludens-2 (ZO-2) is a protein present at the tight junction and nucleus of epithelial cells. ZO-2 represses the transcription of genes regulated by the Wnt/β-catenin pathway. This pathway plays a critical role in podocyte injury and proteinuria. Here we analyze if the over-expression of ZO-2 in the glomerulus, by hydrodynamics transfection, prevents podocyte injury mediated by the Wnt/β-catenin pathway in the mouse model of adriamycin (ADR) nephrosis. By immunofluorescence and immunogold electron microscopy, we show that ZO-2 is present in mice glomerulus, not at the slit diaphragms where nephrin concentrates, but at the cytoplasm and processes of podocytes. Our results indicate that in the glomeruli of mice treated with ADR, ZO-2 over-expression increases the amount of phosphorylated β-catenin, inhibits the expression of the transcription factor snail, prevents nephrin and podocalyxin loss, reduces podocyte effacement and massive fusions, restrains proteinuria and maintains creatinine clearance. These results suggest that ZO-2 could be a new target for the regulation of hyperactive Wnt/β-catenin signaling in proteinuric kidney diseases.
Authors:
Pablo Bautista-Garcia; Jose L Reyes; Dolores Martin; Maria C Namorado; Bibiana Chavez-Munguia; Elizabeth Soria-Castro; Otmar Huber; Lorenza Gonzalez-Mariscal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-3
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  -     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Center for Research and Advanced Studies.
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