Podocyte Wnt/ß-catenin pathway is activated by integrin-linked kinase in clinical and experimental focal segmental glomerulosclerosis.

Abstract:

BACKGROUND:Changes in podocyte phenotype and function are characteristic of proteinuric glomerular diseases. Integrin-linked kinase (ILK) functions as a common downstream effector in proteinuric diseases. In addition, ILK was shown to interact with the Wnt signaling pathway. Here, we investigated ILK expression as well as its involvement with the Wnt signaling pathway in renal biopsies of patients with primary focal segmental glomerulosclerosis (FSGS), and in a correspondent in vivo model of podocyte lesion. METHODS:Biopsies from 37 patients with primary FSGS were evaluated by immunohistochemistry for ILK, phosphorylated GSK-3ß (pGSK-3ß) and ß-catenin expression. As experimental model, male Wistar rats received 5 injections of puromycin aminonucleoside (PAN) at 2-week intervals, and their kidneys were evaluated for ILK, P-cadherin and pAkt expression as well as ß-catenin and LEF-1 colocalization. RESULTS:Patients presented de novo ILK expression and pGSK-3ß in podocytes. In animals, there was an increase in gene and protein expression of ILK, mainly detected in the podocytes, as well as increased protein expression of pAkt compared with controls. ß-Catenin translocated to the nuclei of podocytes in animals and patients. ß-Catenin colocalized with LEF-1 in the nuclei of podocytes of animals. Gene expression of ß-catenin and P-cadherin in PAN rats was lower compared with controls. CONCLUSIONS:Our findings suggest that activation of ILK activated the Wnt signaling pathway in damaged podocytes. This phenomenon could have an important role in development and/or progression of clinical and experimental FSGS.

journal_name

J Nephrol

journal_title

Journal of nephrology

authors

Naves MA,Requião-Moura LR,Soares MF,Silva-Júnior JA,Mastroianni-Kirsztajn G,Teixeira VP

doi

10.5301/jn.5000017

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

401-9

issue

3

eissn

1121-8428

issn

1724-6059

pii

9304A89E-1033-494C-9C94-8560042C55E8

journal_volume

25

pub_type

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