Rele of MAP kinases in normal and abnormal renal development

点击翻译按钮获取中文摘要

We investigated the role of mitogen-activated protein kinase (MAPK) family, a critical enzyme in cellular signaling, in normal and abnormal renal development. Extracellular signal-regulated kinase (ERK), p38 MAPK (p38), and MAPK phosphatase-1 (MKP-1) are strongly expressed in the developing kidney, and JNK is detected predominantly in the adult kidney. Both the temporal and spatial expression of ERK coincides with the maturation of the kidney.We next investigated the role of ERK and p38 in organ culture system using ERK or p38 inhibitors. Both ERK and p38 are demonstrated to be necessary for renal development. ERK appears to play a role in nephrogenesis and p38 for kidney growth and nephrogenesis.Next the role of MAPKs in abnormal kidney development was examined. p38 is ectopically expressed, and JNK is downregulated in dysplastic epithelia of human multicystic dysplastic kidney. Furthermore, dysplastic epithelia are exclusively positive for ERK and P-ERK. Activated p38 and ERK may med … More iate hyperproliferation of dysplastic tubules resulting in cyst formation/whereas downregulated JNK expression may be the cause or the result of an undifferentiated state of dysplastic epithelia. The same pattern of MAPK dysregulation was observed in the mouse model of polycystic kidney disease.Fibroblast growth factor 2 (FGF2) prevents apoptosis and stimulates proliferation of metanephric mesenchymal cells (MMCs). The cellular signaling of FGF2 in MMCs has not yet been clarified. We therefore investigated whether p38 and ERK were involved in FGF2-induced mitogenesis and migration of MMCs. Our results showed that both p38 and ERK are activated by FGF2 and mediate FGF2-induced mitogenesis and migration of MMCs.Since dysplastic kidneys are commonly associated with fetal urinary tract obstruction, we investigated the expression-of MAPKs in ovine model of fetal urinary tract obstruction. Similarly to human multicystic dysplastic kidney and mouse polycystic kidney. p38, ERK are upregulated and JNK was downregulated in cyst epithelia and dysplastic tubules.In conclusion, we have demonstrated that MAPKs play an important role in normal and abnormal kidney development. Less