Expression of bcl-2 and bax in regenerating rat renal tubules following ischemic injury.

To define potential roles for bcl-2 and bax in adult kidney as regulators of regeneration, their expressions were characterized postischemic injury. A 2.1-fold increase in levels of renal bcl-2 mRNA occurred within 24 h of injury relative to levels in kidney of sham-operated control rats. The levels of bcl-2 mRNA remained elevated for 3 days but returned to baseline by day 5 postischemia. In situ hybridization of kidneys from sham-operated rats demonstrated faint expression of bcl-2 mRNA localized diffusely throughout the nephron. After renal injury, the expression of bcl-2 mRNA was markedly enhanced in regenerating proximal tubule cells relining the basement membrane. Immunohistochemistry showed a similar localization for bcl-2 protein. Levels of bax mRNA in kidney were elevated beginning at 24 h postischemia and remained elevated for 7 days postinjury. Bax mRNA and bax protein were colocalized to regenerating proximal tubules postischemia and were prominently expressed in papillary proliferations. We conclude that the expressions of bcl-2 and bax in kidney are enhanced in a predictable pattern following acute ischemic injury. Our findings suggest that these regulators of apoptosis play key roles in the process of repair of the damaged proximal tubule postischemia.