Bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth.
Bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth.
复制标题
DOI：
10.1371/journal.pone.0073554
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yanagita M
中科院分区：
文献类型：
--
作者：
Tomita M;Asada M;Asada N;Nakamura J;Oguchi A;Higashi AY;Endo S;Robertson E;Kimura T;Kita T;Economides AN;Kreidberg J;Yanagita M
肾单位（肾脏的功能单位）的数量因人而异。出生时肾单位数量低与高血压风险和肾功能不全的进展有关。胚胎发生过程中决定肾单位数量的分子机制尚未阐明。骨形态发生蛋白 7 (Bmp7) 的种系敲除会导致肾祖细胞大量凋亡以及肾发生早期阶段的缺陷。这种表型妨碍了对肾发生后期 Bmp7 功能的分析。在本研究中，利用Bmp7的条件无效等位基因与全身可诱导的Cre删除小鼠相结合，使我们能够分析肾脏发育过程中所需时间点的Bmp7功能，并发现Bmp7抑制祖细胞向肾单位过早分化的新功能。肾脏发育开始后，体内系统性敲除 Bmp7 会导致肾脏祖细胞过早分化为肾单位，此外还会导致祖细胞显着凋亡。我们还证实，在肾外植体培养中体外敲除 Bmp7 会导致祖细胞群加速分化。最后，我们利用集落形成试验证明 Bmp7 抑制肾祖细胞的上皮化和分化。这些结果表明，Bmp7抑制祖细胞早熟分化的功能及其对祖细胞的抗凋亡作用协同维持肾祖细胞库处于未分化状态，并决定出生时肾单位的数量。
The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.
登录
查看更多内容
影响因子：
2.3
作者：
Ross, A.;Munger, S.;Capel, B.
通讯作者：
Capel, B.
影响因子：
2.7
作者：
Boyle, Scott;Misfeldt, Andrew;de Caestecker, Mark
通讯作者：
de Caestecker, Mark
影响因子：
10.5
作者：
DUDLEY, AT;LYONS, KM;ROBERTSON, EJ
通讯作者：
ROBERTSON, EJ
影响因子：
4.8
作者：
Gregory, KE;Ono, RN;Sakai, LY
通讯作者：
Sakai, LY
影响因子：
4.6
作者：
Osafune, K;Takasato, M;Nishinakamura, R
通讯作者：
Nishinakamura, R