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 Nephroljournal_title
Journal of nephrologyauthors
Naves MA,Requião-Moura LR,Soares MF,Silva-Júnior JA,Mastroianni-Kirsztajn G,Teixeira VPdoi
10.5301/jn.5000017subject
Has Abstractpub_date
2012-05-01 00:00:00pages
401-9issue
3eissn
1121-8428issn
1724-6059pii
9304A89E-1033-494C-9C94-8560042C55E8journal_volume
25pub_type
杂志文章abstract:BACKGROUND:Proteinuria results from increased glomerular permeability and is associated with retraction and effacement of the highly specialized interdigitating podocyte foot processes. In podocytes (glomerular epithelial cells [GECs]), p130Cas localizes diffusely to the cytoplasm and connects focal adhesion proteins a...
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2006-09-01 00:00:00
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doi:
更新日期:2005-09-01 00:00:00
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更新日期:2012-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2012-01-01 00:00:00
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更新日期:2003-11-01 00:00:00
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更新日期:1998-11-01 00:00:00
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pub_type: 临床试验,杂志文章
doi:
更新日期:2000-09-01 00:00:00
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更新日期:2015-06-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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pub_type: 杂志文章,多中心研究
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