Helsinki Institute of Life Science, University of Helsinki, FIN-00014 Helsinki, Finland.
Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland.
Int J Mol Sci. 2019 Apr 10;20(7):1779. doi: 10.3390/ijms20071779.
Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects derived from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding of how mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activity contributes to the regulation of ureteric bud branching morphogenesis, which dictates the final size, shape, and nephron number of the kidney. Recent studies also demonstrate that the MAPK/ERK pathway is directly involved in nephrogenesis, regulating both the maintenance and differentiation of the nephrogenic mesenchyme. Interestingly, aberrant MAPK/ERK signaling is linked to many cancers, and recent studies suggest it also plays a role in the most common pediatric renal cancer, Wilms' tumor.
先天性肾及尿路畸形（CAKUT）是一种常见的出生缺陷，源于胚胎发生过程中肾脏分化异常。CAKUT 是儿童终末期肾病和慢性肾脏病的主要病因，但遗传病因仍很大程度上未得到解决。在这里，我们将讨论对丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）活性如何有助于调节输尿管芽分支形态发生的理解进展，该过程决定了肾脏的最终大小、形状和肾单位数量。最近的研究还表明，MAPK/ERK 通路直接参与肾发生，调节肾间充质的维持和分化。有趣的是，异常的 MAPK/ERK 信号与许多癌症有关，最近的研究表明它也在最常见的小儿肾癌——威尔姆斯瘤中发挥作用。
