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

Abstract

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 alpha1, alpha2, and beta1 in RPTC was not altered on day 1 after sublethal injury by S-(1,2-dichlorovinyl)-L-cysteine (DCVC). On day 6, expression of alpha1 and beta1 subunits remained unchanged, whereas a 2.2-fold increase in alpha2 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 microM) or exogenous collagen IV (50 microg/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 beta1 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.

Involvement of matrix metalloproteinase-2 in the development of renal interstitial fibrosis in mouse obstructive nephropathy

“…[32][33][34][35][36] In the cell-ECM interactions, integrin-mediated signals from the ECM are transduced by ILK, a cytoplasmic serine-threonine kinase, and the activated ILK upregulate the both b-catenin Figure 7 The expression of S100A4 (a, Â 800), vimentin (b, Â 800), a-smooth muscle actin (aSMA) (c, Â 800), and heat shock protein-47 (HSP-47, Â 800) (d) in renal tubules at day 14 post-unilateral ureteral obstruction (UUO), and double immunostaining with S100A4 (green) and aSMA (red) before UUO (e) and at day 14 post-UUO in MMP-2 þ / þ mice (f), MMP-2 À/À mice (g), and MMP-2 þ / þ mice treated with minocycline (h) (e-h, Â 600). S100A4 þ , vimentin þ , aSMA þ , or HSP-47 þ cells were present in damaged renal tubules (arrowhead in panels a-d).…”

Investigation into the Distribution of Total, Free, Peptide-bound, Protein-bound, Soluble-and Insoluble-Collagen Hydroxyproline in Various Bovine Tissues

“…Earlier studies have shown the presence of type I collagen in the bovine renal cortex where the hydroxylation of prolyl residues is higher that lysine (Bentley and Hanson, 1969). Recent studies (Nony et al, 2001) have shown that collagen IV is found in the renal proximal tubular cell basement membrane and it mediates renal development and function. The collagen in the lungs may be contributed from the surfactant protein A of the alveolus (Khubchandani and Snyder, 2001).…”

Role of Matrix Metalloproteinase-2 in Recovery after Tubular Damage in Acute Kidney Injury in Mice

“…The potential role of extracellular matrix proteins in tubular regeneration and repair has also been considered [10]. A recent study reported that stimulation of collagen IV deposition and subsequent cellular binding to collagen IV is sufficient to stimulate repair of injured renal tubular cells and promote the return of cell polarity as well as differentiation that can subsequently enhance the recovery of physiological functions [34,35]. MMPs are involved in the regulation of cell-extracellular matrix interactions [23].…”

“…In AKI, proliferation of the remaining tubular epithelial cells, migration of regenerated epithelial cells to the denuded areas, and differentiation of regenerated epithelial cells within the damaged tubules following injury are important for the structural and functional recovery of the kidney [10,11,34,35]. In the present study, recovery of the damaged tubules in MMP-2 -/- and MMP inhibitor-treated MMP-2 +/+ mice was incomplete, probably due to impaired proliferation, migration or differentiation of regenerated epithelial cells in the damaged tubules.…”