Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney.
Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney.
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发表时间：
2002-11
期刊：
影响因子：
4.6
通讯作者：
Jing Yu;T. Carroll;A. McMahon
中科院分区：
文献类型：
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作者：
Jing Yu;T. Carroll;A. McMahon
输尿管芽上皮的信号传导对于肾脏发育过程中后肾间充质的存活、增殖和分化至关重要。大多数关于输尿管信号传导的研究都集中在近端、分支的输尿管上皮上。我们证明，音刺猬表达在远端的输尿管上皮，无分支的髓质集合管，并继续进入输尿管上皮-连接肾脏和膀胱的尿流出道。patched 1、音刺猬受体和远端集合管和输尿管周围间充质中信号通路的下游靶基因的上调表明音刺猬充当旁分泌信号。体内和体外分析表明，音刺猬促进间充质细胞增殖，调节平滑肌祖细胞分化的时间，并通过其剂量依赖性抑制平滑肌形成来设定间充质分化的模式。此外，我们还表明，骨形态发生蛋白4是在肾间质和输尿管间质中的音刺猬信号的下游靶基因，但不介导音刺猬在控制间质增殖的作用。
Signaling by the ureteric bud epithelium is essential for survival, proliferation and differentiation of the metanephric mesenchyme during kidney development. Most studies that have addressed ureteric signaling have focused on the proximal, branching, ureteric epithelium. We demonstrate that sonic hedgehog is expressed in the ureteric epithelium of the distal, non-branching medullary collecting ducts and continues into the epithelium of the ureter -- the urinary outflow tract that connects the kidney with the bladder. Upregulation of patched 1, the sonic hedgehog receptor and a downstream target gene of the signaling pathway in the mesenchyme surrounding the distal collecting ducts and the ureter suggests that sonic hedgehog acts as a paracrine signal. In vivo and in vitro analyses demonstrate that sonic hedgehog promotes mesenchymal cell proliferation, regulates the timing of differentiation of smooth muscle progenitor cells, and sets the pattern of mesenchymal differentiation through its dose-dependent inhibition of smooth muscle formation. In addition, we also show that bone morphogenetic protein 4 is a downstream target gene of sonic hedgehog signaling in kidney stroma and ureteral mesenchyme, but does not mediate the effects of sonic hedgehog in the control of mesenchymal proliferation.