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

Autor(es)

Naves, Marcelo A. ; Requiao-Moura, Lucio R. ; Soares, Maria F. ^[1] ; Silva-Junior, Jose A. ^[1] ; Mastroianni-Kirsztajn, Gianna ^[2] ; Teixeira, Vicente P. C. ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo UNIFESP, Dept Pathol, BR-04023900 Sao Paulo - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Glomerulopathy Sect, Div Nephrol, Dept Med, BR-04023900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEPHROLOGY; v. 25, n. 3, p. 401-409, MAY-JUN 2012.
• Citações Web of Science: 16

Resumo

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-3 beta (pGSK-3 beta) and beta-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 beta-catenin and LEF-1 colocalization. Results: Patients presented de novo ILK expression and pGSK-3 beta 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. beta-Catenin translocated to the nuclei of podocytes in animals and patients. beta-Catenin colocalized with LEF-1 in the nuclei of podocytes of animals. Gene expression of beta-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. (AU)

• Processo FAPESP: 05/01202-0 - Ativação da proteinoquinase acoplada à integrina (ILK) e via de sinalização WNT após lesão do podócito em doença proteinúrica: um possível mecanismo patogenético
• Beneficiário: Vicente de Paulo Castro Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular