MAP kinase in renal development.

Abstract

Among mitogen-activated protein kinase (MAPK) family members, ERK promotes proliferation or differentiation, whereas JNK and p38 are thought to inhibit cell growth and induce apoptosis. During renal development, large-scale proliferation and apoptosis occur. We investigated the temporal and spatial expression patterns of MAPK and its phosphatase MKP-1 as well as the role of ERK and p38 during kidney development. Western blot analysis and immunohistochemistry were performed in the developing and mature kidney of the rat. Rat metanephroi were cultured from 15-day-old embryos, and exposed to inhibitors of MEK, an activator of ERK, PD98059, U0126 or a p38 inhibitor, SB203580 24-120 h after the start of culture. Growth of metanephroi was measured by surface area and thymidine incorporation. Ureteric buds and glomeruli were identified by labelling with Dolichos biflorus lectin and peanut agglutinin, respectively. The expression of ERK and p38 was high in the developing kidney. On the other hand, JNK was expressed abundantly in the adult kidney. Immunohistochemical studies revealed that the spatial expression of ERK coincided with the maturation of the kidney. p38 and MKP-1 were expressed uniformly. Growth of metanephroi was significantly inhibited by SB203580 but not by PD98059 or U0126. Ureteric bud branching was not affected by SB203580 or MEK inhibitors. Glomerular number was markedly reduced by SB203580 and to a lesser extent by U0126. ERK, p38 and MKP-1 are strongly expressed in the developing kidney, and JNK is detected predominantly in the adult kidney. ERK appears to play a role in nephrogenesis and p38 in kidney growth and nephrogenesis.