TGF-beta1-mediated inhibition of HK-2 cell migration.
Restoration of proximal tubular cell (PTC) integrity and function after ischemic injury involves cell proliferation and migration. Hypoxia is a known stimulus for PTC TGF-beta1 synthesis. This study examines the effect of TGF-beta1 on PTC migration. A model of PTC injury was used consisting of mechanically wounding a monolayer of HK2 cells followed by repopulation of the denuded area by time lapse photomicroscopy. Repopulation was the result of cell migration but not proliferation. Addition of TGF-beta1 led to a marked inhibition of cell migration increased expression of paxillin and vincullin and their incorporation into dense focal adhesion plaques. This was associated with increased association of focal adhesion components with the f-actin cytoskeleton. There was also increased beta3 integrin expression and increased synthesis of the matrix component fibronectin. The effect on migration and focal adhesion reorganisation was abrogated by inhibitors of the RhoA downstream target ROCK, suggesting that signaling events resulting from altered beta3 integrin expression initiate the TGF-beta1 response. These results suggest that, by inhibition of cell migration, increased expression of TGF-beta1 after ischemia delays recovery of proximal tubule structure and function. We speculate that this may contribute to permanent alteration in renal tubular function after severe ischemic injury.
Tian
Ya-Chung
YC
Institute of Nephrology, University of Wales College of Medicine, Cardiff, Wales.
Phillips
Aled O
AO
D002450:Cell Communication / Q000187:drug effects; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014638:Vanadates / Q000494:pharmacology
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014638:Vanadates