Decreased expression of β1 integrin in enteric neural crest cells of the endothelin receptor B null mouse model.
Decreased expression of β1 integrin in enteric neural crest cells of the endothelin receptor B null mouse model.
复制标题
降低内皮素受体 B 缺失小鼠模型肠神经嵴细胞中 β1 整合素的表达。
DOI：
10.1007/s00383-019-04578-y
复制
发表时间：
2020
影响因子：
1.8
通讯作者：
Yamataka A.
中科院分区：
文献类型：
--
作者：
Nakazawa-Tanaka N;Miyahara K;Fujiwara N;Ochi T;Sueyoshi R;Nojiri S;Akazawa C;Urao M;Yamataka A.
肠神经嵴源性细胞（ENCC）与周围肠道微环境如细胞外基质（ECM）的相互作用对肠神经系统（ENS）的发育起着重要的调控作用。整合素是ECM分子如层粘连蛋白的主要受体，已报道其参与先天性巨结肠的发病机制。方法建立内皮素受体B（Ednr B）基因敲除（KO）小鼠模型，以Sox 10-Venus阳性Ednrb野生型（WT）小鼠为对照。于E13.5和E15.5分别取小肠、近端结肠和远端结肠，采用免疫组化和真实的实时RT-PCR检测肠组织β1整合素的表达。分离在E11.5解剖的肠细胞并培养2天。静脉阳性ENCC与β1整合素和Tuj-1，这是一个标记neurons.ResultsThe β1整合素的表达没有显着差异KO和WT在肠道检查的所有部分。然而，与WT相比，KO中分离的ENCC中的β1整合素表达显著降低。KO小鼠的平均阈值面积为42.98 ± 17.47%，WT小鼠为73.53 ± 13.77%（P< 0.001）。我们的研究结果表明，整合素及其配体之间的相互作用受损可能会干扰正常ENS的发展，导致无神经节结肠。
BackgroundInteractions between enteric neural crest-derived cells (ENCC) and the surrounding intestinal microenvironment, such as the extracellular matrix (ECM), are critical for regulating enteric nervous system (ENS) development. Integrins are the major receptors for ECM molecules, such as laminin, which have been reported to be involved in the pathogenesis of Hirschsprung’s disease. In this study, we examined the expression of β1 integrin in the endothelin receptor B (Ednrb) knock out (KO) mouse gut, which presents with an aganglionic colon.MethodsASox10-Venus-positiveEdnrbKO mouse, where ENCC is labeled with fluorescent protein, ‘Venus’, was created.Sox10-Venus-positiveEdnrbwild type (WT) were used as controls. Small intestine, proximal colon and distal colon were dissected on E13.5 and E15.5 and β1 integrin expression of the gut tissue was examined by immunohistochemistry and real time RT-PCR. The cells of the gut dissected on E11.5 were isolated and cultured for 2 days. Venus-positive ENCC were immunostained with β1 integrin and Tuj-1, which is a marker for neurons.ResultsThe expression of β1 integrin was not significantly different between KO and WT in all parts of the gut examined. However, the β1 integrin expression in the isolated ENCC was significantly decreased in KO compared to WT. The average threshold area was 42.98 ± 17.47% in KO and 73.53 ± 13.77 in WT (p< 0.001).ConclusionsWe demonstrated that β1 integrin expression was specifically decreased in ENCC inEdnrbKO mice. Our results suggest that impaired interaction between integrin and its ligands may disturb normal ENS development, resulting in an aganglionic colon.