title: 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.
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Naves
authors.forename: Lúcio R
authors.initials: LR
authors.lastname: Requião-Moura
authors.forename: Maria F
authors.initials: MF
authors.lastname: Soares
authors.forename: José A
authors.initials: JA
authors.lastname: Silva-Júnior
authors.forename: Gianna
authors.initials: G
authors.lastname: Mastroianni-Kirsztajn
authors.forename: Vicente P C
authors.initials: VP
authors.lastname: Teixeira
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D050199:Podocytes / Q000201:enzymology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011692:Puromycin Aminonucleoside; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D015820:Cadherins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D051821:Lymphoid Enhancer-Binding Factor 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011692:Puromycin Aminonucleoside; D051153:Wnt Proteins; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; C497575:Lef1 protein, rat