title: Troglitazone induces extracellular matrix and cytoskeleton remodeling in mouse collecting duct cells.
abstract: Peroxisome proliferator-activated receptor (PPARγ) has been shown to have a protective role in the nephron through its ability to inhibit a transforming growth factor- (TGF-β) mediated fibrotic response. In contrast, PPARγ was also shown to induce a mesenchymal transformation in epithelial intestinal cells. A fibrotic response in the collecting duct has only recently been established; however, the entire collecting duct has not been fully examined. Inner medullary collecting duct cells (IMCD-K2) and mouse cortical collecting duct cells (M1), representing the cortical and medullary collecting duct, were exposed to 5-10 μM troglitazone for 24 hours. Troglitazone resulted in an elongated morphology, 60% decreases in E-cadherin and β-catenin, a 35% decrease in α-catenin, and a 1.5-fold increase in fibronectin. These effects were not reversed with PPARγ antagonists or affected with PPARγ overexpression. Our results indicate that troglitazone induced a mesenchymal-like transformation in M1 and IMCD-K2 epithelial cells independently of PPARγ.
authors.affiliation: Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Jaime
authors.initials: J
authors.lastname: Corinaldi
authors.forename: Rania
authors.initials: R
authors.lastname: Nasrallah
authors.forename: Jordan
authors.initials: J
authors.lastname: Clark
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paris
authors.forename: Pedro
authors.initials: P
authors.lastname: Miura
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hébert
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002461:Cell Line, Transformed; D048430:Cell Shape / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D047495:PPAR gamma / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: D000199:Actins; D015820:Cadherins; D051177:Catenins; D002839:Chromans; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D047495:PPAR gamma; D045162:Thiazolidinediones; C544013:alpha-smooth muscle actin, mouse; D000077288:Troglitazone