Tsujimura Taro, Idei Mana, Yoshikawa Masahiro, Takase Osamu, Hishikawa Keiichi
Taro Tsujimura, Mana Idei, Masahiro Yoshikawa, Osamu Takase, Keiichi Hishikawa, Department of Advanced Nephrology and Regenerative Medicine, Division of Tissue Engineering, University of Tokyo Hospital, Tokyo 113-8655, Japan.
World J Stem Cells. 2016 Sep 26;8(9):288-96. doi: 10.4252/wjsc.v8.i9.288.
The gene encoding bone morphogenetic protein-7 (Bmp7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of Bmp7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of Bmp7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases.
编码骨形态发生蛋白7(Bmp7)的基因在胚胎发育中的肾脏以及成年后的成熟器官中均有表达。在肾脏发育过程中,Bmp7的表达对于确定器官内肾单位的最终数量和合适大小至关重要。分泌的BMP7作用于肾单位祖细胞以发挥其双重功能:维持和扩大祖细胞群体,并使其具备响应分化信号的能力,每种功能都依赖于不同的信号通路。有趣的是,在成年器官中,BMP7与肾脏损伤的保护和修复有关。向肾脏疾病动物模型外源性给予重组BMP7已显示出在对抗损伤引起的炎症、凋亡和纤维化方面具有良好效果。尽管Bmp7的表达模式已得到充分描述,但其调控机制仍不清楚,并且BMP7的分泌位点影响其在肾脏发育和疾病中功能的过程尚未得到评估。了解调控机制将为更好地洞察BMP7的作用以及实现对基因表达的理想控制作为肾脏疾病的治疗策略铺平道路。