EXPRESSION OF BCL-2 AND BAX IN REGENERATING RAT RENAL TUBULES FOLLOWING ISCHEMIC-INJURY

To define potential roles for bcl-2 and bar in adult kidney as regulat ors of regeneration, their expressions were characterized postischemic injury. A 2.1-fold increase in levels of renal bcl-2 mRNA occurred wi thin 24 h of injury relative to levels in kidney of sham-operated cont rol rats. The levels of bcl-2 mRNA remained elevated for 3 days but re turned to baseline by day 5 postischemia. In situ hybridization of kid neys from sham-operated rats demonstrated faint expression of bcl-2 mR NA localized diffusely throughout the nephron. After renal injury, the expression of bcl-2 mRNA was markedly enhanced in regenerating proxim al tubule cells relining the basement membrane. Immunohistochemistry s howed a similar localization for bcl-2 protein. Levels of bar mRNA in kidney were elevated beginning at 24 h postischemia and remained eleva ted for 7 days postinjury. Bax mRNA and bar protein were colocalized t o regenerating proximal tubules postischemia and were prominently expr essed in papillary proliferations. We conclude that the expressions of bcl-2 and bar in kidney are enhanced in a predictable pattern followi ng acute ischemic injury. Our findings suggest that these regulators o f apoptosis play key roles in the process of repair of the damaged pro ximal tubule postischemia.