Midkine rescues Wilms' tumor cells from cisplatin-induced apoptosis: regulation of Bcl-2 expression by Midkine.

Midkine (MK) is a heparin-binding growth factor involved in diverse biological phenomena, e.g. neuronal survival, carcinogenesis, and tissue repair. MK expression is detected mainly in the kidney in adult mice. In this study, we show that, at a dose that can induce recoverable renal damage and induce apoptosis, cisplatin (CDDP) transiently suppressed MK expression in mouse kidney. In vitro, CDDP suppressed MK expression and induced apoptosis in cultured G401 cells, a Wilms' tumor cell line. Exogenous MK protein partially rescued G401 cells from CDDP-induced apoptosis. MK enhanced the expression of Bcl-2, but not that of Bcl-x(L), in G401 cells in a dose-dependent manner, and it prevented the Bcl-2 reduction due to CDDP. Moreover, Bcl-2 expression in mouse kidney was also transiently suppressed by CDDP treatment, the expression profile being similar to that of MK. These results imply that MK exerts cytoprotective activity toward a damaging insult, presumably at least in part through enhancement of the expression of Bcl-2.