Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation.
Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation.
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DOI：
10.1016/j.diff.2010.02.002
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发表时间：
2010-04
期刊：
影响因子：
2.9
通讯作者：
Baskin, Laurence
中科院分区：
文献类型：
--
作者：
Cao, Mei;Tasian, Gregory;Wang, Ming-Hsien;Liu, Benchun;Cunha, Gerald;Baskin, Laurence
从膀胱间充质诱导平滑肌分化依赖于来自尿路上皮的信号。我们假设Sonic hedgehog(Shh)是一种尿路上皮信号，可以促进膀胱间充质细胞的增殖，诱导膀胱平滑肌分化。用0.02M EDTA孵育完整膀胱(IB)，显微解剖去除尿路上皮，分离出膀胱间充质(BLM)。IB和BLM在Shh缺乏的培养液中培养，或BLM在添加Shh(480 NM)的培养液中培养72h，IB在含有不同浓度Shh(0、48和480 nM)的培养液中培养72h。妊娠FVB小鼠于胚胎第12.5天安乐死，取胎儿膀胱。使用了两种实验方案：通过连续切片来确定样本的大小。胰酶消化后进行细胞计数。免疫组织化学方法检测血管平滑肌特异性蛋白的表达。用免疫印迹法检测α-肌动蛋白的表达。培养72小时后，所有标本均存活，无Shh培养的BLM存活，但不生长或发生平滑肌分化。不加Shh培养的IB和加Shh培养的BLM在72h生长并表达平滑肌蛋白，加Shh培养的IB较未加Shh培养的IB体积大，细胞数多(P均<0.05)。将Shh浓度从48nM增加到480nM并没有改变膀胱大小、细胞计数或α-肌动蛋白的表达水平。培养前IB不表达α-肌动蛋白。在缺乏Shh的培养液中培养IB后，除粘膜下层外，α-肌动蛋白在整个间充质中均可检测到。48nM Shh培养后IB黏膜下层变薄，480 nM Shh培养后平滑肌完全消失。在胎鼠膀胱中，尿路上皮源性Shh是间充质细胞增殖和平滑肌分化所必需的。ShH浓度影响间充质细胞的增殖和膀胱平滑肌的构型。
Induction of smooth muscle differentiation from bladder mesenchyme depends on signals that originate from the urothelium. We hypothesize Sonic hedgehog (Shh) is the urothelial signal that promotes bladder mesenchymal proliferation and induces bladder smooth muscle differentiation. Bladder mesenchyme (BLM) was isolated by incubating intact bladders (IB) in 0.02 M EDTA and then removing the urothelium by microdissection. IB and BLM were cultured in Shh-deficient media or BLM was cultured in Shh-supplemented (480 nM) media for 72 h. IB were cultured for 72 h in media containing different concentrations of Shh (0, 48, and 480 nM). Pregnant FVB mice were euthanized on embryonic day (E) 12.5 and fetal bladders were harvested. Two experimental protocols were utilized: Specimens were sized by serial sectioning. Cell counts were performed after trypsin digestion. Immunohistochemistry was performed to detect smooth muscle-specific protein expression. α-Actin expression was quantified using Western blot. All specimens were viable at 72 h. BLM cultured without Shh survived but did not grow or undergo smooth muscle differentiation. IB cultured without Shh and BLM cultured with Shh grew and expressed smooth muscle proteins at 72 h. IB cultured with Shh were larger and contained more cells than IB cultured without Shh (all p <0.05). Increasing Shh concentration from 48 to 480 nM did not change bladder size, cell counts, or the level of α-actin expression. Prior to culture, IB did not express α-actin. After culture of IB in Shh-deficient media, α-actin was detected throughout the mesenchyme except in the submucosal layer. The IB submucosa was thinner after culture with 48 nM Shh and smooth muscle completely obliterated the submucosa after culture with 480 nM Shh. In fetal mouse bladders, urothelium-derived Shh is necessary for mesenchymal proliferation and smooth muscle differentiation. Shh concentration affects mesenchymal proliferation and patterning of bladder smooth muscle.
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影响因子：
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