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 biologi cal phenomena, e.g. neuronal survival, carcinogenesis, and tissue repair. M K 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 induc e apoptosis, cisplatin (CDDP) transiently suppressed MK expression in mouse kidney. In vitro, CDDP suppressed MK expression and induced apoptosis in c ultured G401 cells, a Wilms' tumor cell line, Exogenous MK protein partiall y rescued G401 cells ii om CDDP-induced apoptosis, MK enhanced the expressi on of Bcl-2, but not that of Bcl-x(L), in G401 cells in a dose-dependent ma nner, and it prevented the Bcl-2 reduction due to CDDP, Moreover, Bcl-2 exp ression in mouse kidney was also transiently suppressed by CDDP treatment, the expression profile being similar to that of MK, These results imply tha t MK exerts cytoprotective activity toward a damaging insult, presumably at least in part through enhancement of the expression of Bcl-2.