Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype
Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype
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DOI：
10.1016/s0016-5085(99)70560-3
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发表时间：
1999-07-01
期刊：
影响因子：
29.4
通讯作者：
Sanders, KM
中科院分区：
文献类型：
--
作者：
Torihashi, S;Nishi, K;Sanders, KM
背景与目的：Cajal间质细胞（Interstitial cells of Cajal， ICC）作为起搏器细胞和肠神经系统到胃肠道肌肉的神经传递介质。ICC由表达c-Kit的间充质细胞发育而来，Kit受体的信号传导是ICC正常发育所必需的。我们研究了Hit受体阻断后功能发育的ICC的命运，以确定ICC是否经历细胞死亡或细胞表型是否被改变。还对未开发的国际商会的命运进行了调查。方法：小鼠出生后8天给予中和性抗kit单克隆抗体（ACK2）。采用免疫组化和电镜检查小肠ICC组织。同时观察细胞凋亡的发生情况。结果：阻断Kit受体后，ICC几乎从小肠中消失。在ICC正态分布的区域未检测到凋亡。小肠起搏器区剩余的kit免疫阳性细胞呈现出与平滑肌细胞相似的超微结构特征，包括突出的丝束和肌肉特异性中间丝蛋白、desmin和平滑肌肌球蛋白的表达。小鼠的深肌丛ICC通常在出生后发育。当Kit被阻断时，这些细胞的前体仍处于未分化状态。结论：这些数据，以及先前的研究表明，小肠起搏器区域的ICC和纵向肌细胞由相同的kit免疫阳性前体细胞发育而来，表明ICC和平滑肌细胞之间固有的可塑性是由kit依赖性细胞信号调节的。
Background & Aims: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Hit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated. Methods: Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed. Results: When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked. Conclusions: These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.