Vol. 60, Issue 6, 1226-1234, December 2001

Interactions between Collagen IV and Collagen-Binding Integrins in Renal Cell Repair after Sublethal Injury

Paul A. Nony¹ and Rick G. Schnellmann²

Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Recent studies demonstrate that collagen IV selectively promotes the repair of physiological processes in sublethally injured renal proximal tubular cells (RPTC). We sought to further define the mechanisms of cell repair by measuring the effects of toxicant injury and stimulation of repair by L-ascorbic acid-2-phosphate (AscP), exogenous collagen IV, or function-stimulating integrin antibodies on the expression and subcellular localization of collagen-binding integrins (CBI) in RPTC. Expression of CBI subunits ₁, ₂, and ₁ in RPTC was not altered on day 1 after sublethal injury by S-(1,2-dichlorovinyl)-L-cysteine (DCVC). On day 6, expression of ₁ and ₁ subunits remained unchanged, whereas a 2.2-fold increase in ₂ expression was evident in injured RPTC. CBI localization in control RPTC was limited exclusively to the basal membrane. On day 1 after injury, RPTC exhibited a marked inhibition of active Na⁺ transport and a loss of cell polarity characterized by a decrease in basal CBI localization and the appearance of CBI on the apical membrane. On day 6 after injury, RPTC still exhibited marked inhibition of active Na⁺ transport and localization of CBI to the apical membrane. However, DCVC-injured RPTC cultured in pharmacological concentrations of AscP (500 µM) or exogenous collagen IV (50 µg/ml) exhibited an increase in active Na⁺ transport, relocalization of CBI to the basal membrane, and the disappearance of CBI from the apical membrane on day 6. Function-stimulating antibodies to CBI ₁ did not promote basal relocalization of CBI despite stimulating the repair of Na⁺/K⁺-ATPase activity on day 6 after injury. These data demonstrate that DCVC disrupts integrin localization and that physiological repair stimulated by AscP or collagen IV is associated with the basal relocalization of CBI in DCVC-injured RPTC. These data also suggest that CBI-mediated repair of physiological functions may occur independently of integrin relocalization.