Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases.
Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases.
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DOI：
10.4252/wjsc.v8.i9.288
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发表时间：
2016-09-26
影响因子：
4.1
通讯作者：
Hishikawa K
中科院分区：
文献类型：
--
作者：
Tsujimura T;Idei M;Yoshikawa M;Takase O;Hishikawa K
编码骨形态发生蛋白-7 （Bmp7）的基因在胚胎发育中的肾脏和成人成熟器官中表达。在肾脏发育过程中，Bmp7的表达对于决定肾脏中肾单位的最终数量和适当大小至关重要。分泌的BMP7作用于肾元祖细胞，发挥其双重功能：维持和扩大祖细胞群，并为它们提供对分化信号作出反应的能力，每种信号都依赖于不同的信号通路。有趣的是，在成人器官中，BMP7参与了对损伤的保护和再生。重组BMP7外源性给药于肾脏疾病动物模型，在对抗损伤引起的炎症、细胞凋亡和纤维化方面显示出良好的效果。尽管Bmp7的表达模式已经被很好地描述，但其调控机制仍然难以捉摸，Bmp7的分泌位点在肾脏发育和疾病中影响其功能的过程尚未被评估。了解调控机制将为更好地了解BMP7的作用铺平道路，并实现对基因表达的预期控制，作为肾脏疾病的治疗策略。
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.
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