Mesenchymal transition in kidney collecting duct epithelial cells.
Progressive organ damage due to tissue scarring and fibrosis is a paradigm shared by numerous human diseases including chronic kidney disease. The purpose of this study was to confirm the hypothesis that collecting duct (CD) epithelial cells can undergo mesenchymal transition (EMT) in vitro. The mechanism by which CDs undergo EMT is complex and involves both early and late cellular events. Early events include rapid insulin-like growth factor (IGF)-induced Akt and GSK-3beta phosphorylation, associated with early disruption of E-cadherin-beta-catenin membrane colocalization, with translocation of E-cadherin to endosomes, with translocation of beta-catenin to the nucleus, and with an increase in Snail expression. Transforming growth factor-beta1, on the other hand, induced early activation of Smad3 and its translocation to the nucleus, Erk1/2 phosphorylation, and early disruption of membrane E-cadherin localization. The late consequences of these events included a phenotypic transformation of the cells to a mesenchymal morphology with associated increase in vimentin and alpha-smooth muscle actin protein expression and a decrease in total cellular E-cadherin expression, detectable as early as 24 h after stimulation.
Ivanova
Larissa
L
Department of Pediatrics and Child and Family Research Institute, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
Butt
Michael J
MJ
Matsell
Douglas G
DG
D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000037:antagonists & inhibitors; D000071250:Snail Family Transcription Factors; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
D015820:Cadherins; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I