Spatially restricted Hedgehog signalling regulates HGF-induced branching of the adult prostate.
Spatially restricted Hedgehog signalling regulates HGF-induced branching of the adult prostate.
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DOI：
10.1038/ncb3057
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发表时间：
2014-12
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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分支的形态发生被认为是由上皮-间质相互作用所控制的，但分支位置的指定背后的机制在很大程度上仍然不清楚。由于成人前列腺再生小管中新芽部位明显缺乏Hedgehog(HH)反应，我们研究了HH信号在成人前列腺分支形态发生中的作用。我们发现，通路的活性局限于基质细胞，并且其通过遗传或药物操作的减弱导致分支增加。途径活性的降低与肝细胞生长因子(HGF)间质产生的增加相关，我们发现HGF诱导上皮管分支。HH信号对HGF表达的调节是间接的，通过HH诱导的miR-26a和miR-26b的表达，进而下调HGF的表达。因此，前列腺管分支可能起源于HH途径活性较低的区域，这可能与成年后期常见的前列腺增生有关。
Branching morphogenesis is thought to be governed by epithelial-stromal interactions, but the mechanisms underlying specification of branch location remain largely unknown. Prompted by the striking absence of Hedgehog (Hh) response at the sites of nascent buds in regenerating tubules of the adult prostate, we investigated the role of Hh signaling in adult prostate branching morphogenesis. We find that pathway activity is localized to stromal cells, and that its attenuation by genetic or pharmacologic manipulation leads to increased branching. Decreased pathway activity correlates with increased stromal production of Hepatocyte growth factor (Hgf), and we show that Hgf induces epithelial tubule branching. Regulation of Hgf expression by Hh signaling is indirect, mediated by Hh-induced expression of microRNAs miR-26a and miR-26b, which in turn down-regulate expression of Hgf. Prostate tubule branching thus may be initiated from regions of low Hh pathway activity, with implications for the prostatic hyperplasia commonly observed in late adulthood.
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