Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon.
Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon.
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DOI：
10.1111/j.1582-4934.2009.00689.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Huizinga JD
中科院分区：
文献类型：
--
作者：
Wang XY;Albertí E;White EJ;Mikkelsen HB;Larsen JO;Jiménez M;Huizinga JD
Ws/Ws 突变大鼠的结肠显示出起搏器活性受损和抑制性神经传递改变。本研究旨在寻找与这些发现的结构相关性，以解决机制问题。免疫组化和电镜显示，Ws/Ws大鼠结肠中Cajal奥尔巴赫丛相关间质细胞（ICC-AP）显着减少，位于肌下丛的ICC和肌内ICC很少见。超微结构研究显示，所有类型的间质细胞组合并没有总体损失。当观察到 ICC 丢失时，在 AP 水平发现成纤维细胞样 ICC (FL-ICC) 显着增加。免疫电子显微镜证明 FL-ICC 是 c-Kit–，但间隙连接彼此偶联并与 c-Kit+ ICC 偶联；它们与野生型大鼠结肠中的肠神经和通常由 ICC 占据的空间相关，表明它们是不成熟的 ICC。此外，胰岛素样生长因子 1 受体 (Igf1r) 的免疫反应性显着增加，与 CD34 共定位，但与 c-Kit 不共定位。与野生型大鼠结肠相比，Ws/Ws 中发现 Igf1r+/CD34+ 细胞数量显着增加。 Ws/Ws 结肠中的这些 CD34+/Igf1r+ 细胞占据与 FL-ICC 相同的空间。因此，我们提出未成熟 ICC (FL-ICC) 的一个子集由成年祖细胞组成。免疫组织化学显示神经元一氧化氮合酶呈阳性的神经元减少。未成熟ICC的功能和成体祖细胞的再生能力需要进一步研究。这里描述的形态学特征表明，起搏器活性的丧失与未能在 AP 周围形成间质细胞网络无关，而是与未能将该网络发育成功能齐全的起搏器细胞有关。与 Ws 突变相关的氮能神经支配的减少可能是氮能神经元减少的结果。
The colon of Ws/Ws mutant rats shows impairment of pacemaker activity and altered inhibitory neurotransmission. The present study set out to find structural correlates to these findings to resolve mechanisms. In the colon of Ws/Ws rats, interstitial cells of Cajal associated with Auerbach’s plexus (ICC-AP) were significantly decreased and ICC located at the submuscular plexus and intramuscular ICC were rarely observed based on immunohistochemistry and electron microscopy. Ultrastructural investigations revealed that there was no overall loss of all types of interstitial cells combined. Where loss of ICC was observed, a marked increase in fibroblast-like ICC (FL-ICC) was found at the level of AP. Immunoelectron microscopy proved FL-ICC to be c-Kit– but gap junction coupled to each other and to c-Kit+ ICC; they were associated with enteric nerves and occupied space normally occupied by ICC in the wild-type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin-like growth factor 1 receptor (Igf1r) occurred, co-localized with CD34 but not with c-Kit. A significantly higher number of Igf1r+/CD34+ cells were found in Ws/Ws compared to wild-type rat colons. These CD34+/Igf1r+ cells in the Ws/Ws colon occupied the same space as FL-ICC. Hence we propose that a subset of immature ICC (FL-ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase. The functional capabilities of the immature ICC and the regenerative capabilities of the adult progenitor cells need further study. The morphological features described here show that the loss of pacemaker activity is not associated with failure to develop a network of interstitial cells around AP but a failure to develop this network into fully functional pacemaker cells. The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.