Platelet-derived growth factor signals play critical roles in differentiation of longitudinal smooth muscle cells in mouse embryonic gut
Platelet-derived growth factor signals play critical roles in differentiation of longitudinal smooth muscle cells in mouse embryonic gut
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DOI：
10.1111/j.1365-2982.2007.01055.x
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Torihashi, S.
中科院分区：
文献类型：
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作者：
Kurahashi, M.;Niwa, Y.;Torihashi, S.
在小鼠肠道发育过程中，纵向平滑肌细胞(LMC)和Cajal间质细胞(ICC)起源于表达c-Kit的共同前体细胞。近年来，一些起源于肠道平滑肌层的具有c-kit功能增强突变的胃肠道间质瘤，被报道存在血小板衍生生长因子受体α基因的功能增强突变。这些数据增加了PDGF信号通路可能参与LMC发生的可能性。因此，我们采用免疫组织化学和原位杂交的方法研究了胚胎肠道PDGF信号家族的表达模式，并利用一种新的器官培养系统研究了PDGF信号在小鼠肠道平滑肌层发育中的作用。在胚胎发育过程中，环肌层表达PDGF-A，肠系膜神经元表达PDGF-B，LMC和ICC共同前体细胞同时表达PDGF受体α和β。选择性PDGF受体抑制剂AG1295抑制LMC在肠道外植体中的分化。结论：PDGF信号在小鼠胚胎肠道LMC分化过程中起重要作用。
In the development of mouse gut, longitudinal smooth muscle cells (LMC) and interstitial cells of Cajal (ICC) originate from common precursor cells expressing c-Kit. Recently, some gastrointestinal stromal tumours, which develop from smooth muscle layers of the gut and have gain-of-function mutations of c-kit, have been reported to have gain-of-function mutations of platelet-derived growth factor (PDGF) receptor alpha gene. These data raise the possibility that PDGF signalling might be involved in the development of LMC. Therefore, we examined the expression pattern of the PDGF signal family of embryonic gut by immunohistochemistry and in situ hybridization, and investigated the role of PDGF signals in the development of smooth muscle layers in mouse gut using a new organ culture system. During embryonic development, the circular muscle layer expressed PDGF-A, enteric neurons expressed PDGF-B and common precursor cells of LMC and ICC expressed both PDGF receptor alpha and beta. The selective PDGF receptor inhibitor AG1295 suppressed the differentiation of LMC in gut explants. We conclude that PDGF signals play critical roles in the differentiation of LMC in mouse embryonic gut.