Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction.
Renal interstitial fibrosis contributes to the progression of most chronic kidney diseases and is an important pathologic feature of urinary tract obstruction. To study the origin of this fibrosis, we used a fetal non-human primate model of unilateral ureteric obstruction focusing on the role of medullary collecting duct (CD) changes. Obstruction at 70 days gestation (full term approximately 165 days) results in cystic dysplasia with significant medullary changes including loss of the epithelial phenotype and gain of a mesenchymal phenotype. These changes were associated with disruption of the epithelial basement membrane and concomitant migration of transitioning cells presumed responsible for the observed peritubular collars of fibrous tissue. There was an abundance of cells that co-expressed the intercalated cell marker carbonic anhydrase II and smooth muscle actin. These cells migrated through the basement membrane and were significantly reduced in obstructed ducts with peritubular collars. Our studies suggest that fetal urinary tract obstruction results in a CD epithelial-mesenchymal transition contributing to the interstitial changes associated with poor prognosis. This seems restricted to the intercalated cells, which contribute to the expansion of the principal cell population and the formation of peritubular collars, but are depleted in progressive injury.
Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
M J
MJ
Butt
A F
AF
Tarantal
D F
DF
Jimenez
D G
DG
Matsell
D000199:Actins / Q000378:metabolism; D000818:Animals; D024402:Carbonic Anhydrase II / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D008253:Macaca mulatta; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology*
D000199:Actins; D024402:Carbonic Anhydrase II