Glomerular regeneration is delayed in nephritic alpha 8-integrin-deficient mice: contribution of alpha 8-integrin to the regulation of mesangial cell apoptosis.

ABSTRACT

BACKGROUND/AIMS: alpha(8)beta(1)-Integrin is expressed in mesangial cells. In vitro studies suggest a role for alpha(8)-integrin in the regulation of cell proliferation and apoptosis. We tested the hypothesis that alpha(8)-integrin is essential for the healing process after mesangioproliferative glomerulonephritis. METHODS: Mice homozygous for a deletion of the alpha(8)-integrin chain were compared with wild-type mice. To study glomerular healing, we used the habu toxin model of reversible mesangioproliferative glomerulonephritis. Animals received 6 mg/kg habu toxin intravenously; controls received saline only. RESULTS: Early mesangiolysis occurred in wild-type and alpha(8)-integrin-deficient mice. However, mesangiolysis was no longer detectable after 7 days in wild types but persisted after 14 days in alpha(8)-integrin-deficient animals. Mesangial activation marker alpha-smooth muscle actin was detectable only at day 7 in wild-type mice but persisted until day 14 in alpha(8)-integrin-deficient mice. In wild types, glomerular cell proliferation and apoptosis peaked at day 7 and decreased thereafter but remained elevated in alpha(8)-integrin-deficient mice until day 28. In cultivated mesangial cells, alpha(8)-integrin expression was associated with increased cell survival. CONCLUSION: Interactions between alpha(8)-integrin and the mesangial matrix may contribute to healing of glomerular injury by influencing cell proliferation and apoptosis.