Immunohistochemical study on caveolin-1alpha in regenerating process of tubular cells in gentamicin-induced acute tubular injury in rats.

Caveolin-1, a principal component of caveolae, modulates growth signaling, endocytosis, and intracellular transport. We examined the expression of caveolin-1alpha and its relation to cell cycle and caveolin-interacting growth factor receptors in regenerating proximal tubules (PTs) after gentamicin-induced acute renal failure in rats. Caveolin-1alpha appeared in regenerating PTs as early as day 4 after last gentamicin, peaked at days 6 to 8, and showed cytoplasmic pattern after day 8. Immunoelectron microscopy revealed caveolin-1alpha-positive caveolae on the cell membrane and in cytoplasms in regenerating PTs at days 4 to 8 and caveolin-positivity confined to cytoplasms after day 10. The number of PT cells with proliferation markers peaked at day 6 and decreased afterwards as expression of cyclin-dependent kinase inhibitors increased. Platelet-derived growth factor receptor-beta (PDGFR-beta) and epidermal growth factor receptor (EGFR) were colocalized with caveolin-1alpha in proliferating PTs as early as day 4. Phosphorylated EGFR increased at day 8 and afterwards when caveolins dissociated from EGFR or decreased. In case of PDGFR-beta, phosphorylation seemed to be associated with the increase and association of caveolins to the receptors. Our results suggest that transient expression of caveolin-1alpha in early regenerating PTs might contribute to the regenerating process of PTs through modulating growth factor receptors.