Glomerular Regeneration Is Delayed in Nephritic α<sub>8</sub>-Integrin-Deficient Mice: Contribution of α<sub>8</sub>-Integrin to the Regulation of Mesangial Cell Apoptosis

<i>Background/Aims:</i> α₈β₁-Integrin is expressed in mesangial cells. In vitro studies suggest a role for α₈-integrin in the regulation of cell proliferation and apoptosis. We tested the hypothesis that α₈-integrin is essential for the healing process after mesangioproliferative glomerulonephritis. <i>Methods:</i> Mice homozygous for a deletion of the α₈-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. <i>Results:</i> Early mesangiolysis occurred in wild-type and α₈-integrin-deficient mice. However, mesangiolysis was no longer detectable after 7 days in wild types but persisted after 14 days in α₈-integrin-deficient animals. Mesangial activation marker α-smooth muscle actin was detectable only at day 7 in wild-type mice but persisted until day 14 in α₈-integrin-deficient mice. In wild types, glomerular cell proliferation and apoptosis peaked at day 7 and decreased thereafter but remained elevated in α₈-integrin-deficient mice until day 28. In cultivated mesangial cells, α₈-integrin expression was associated with increased cell survival. <i>Conclusion:</i> Interactions between α₈-integrin and the mesangial matrix may contribute to healing of glomerular injury by influencing cell proliferation and apoptosis.