Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility.
Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility.
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平滑肌 Hgs 缺乏导致食管运动受损
DOI：
10.7150/ijbs.12248
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发表时间：
2015
影响因子：
9.2
通讯作者：
Lan Y
中科院分区：
文献类型：
--
作者：
Chen J;Hou N;Zhang C;Teng Y;Cheng X;Li Z;Ren J;Zeng J;Li R;Wang W;Yang X;Lan Y
肝细胞生长因子调节酪氨酸激酶底物（Hgs）作为转运蛋白所需的内体分选复合物的主要成分，参与多种细胞行为。然而，汞在平滑肌细胞（SMCs）的生理作用是迄今为止未知的。本研究采用条件基因敲除的方法，探讨了汞在平滑肌细胞中的体内功能。平滑肌细胞中汞缺乏导致食管进行性扩张，肌层明显变薄。值得注意的是，突变食管显示出对氯化钾和乙酰胆碱刺激的收缩反应性降低。此外，在粘膜和肌肉层中观察到抑制性神经突沿着T淋巴细胞的强烈浸润。结论：SMC中Hgs缺乏导致神经营养因子和炎症相关基因表达紊乱，提示SMC中Hgs缺乏可能是细胞因子和趋化因子过度产生的新来源，这些细胞因子和趋化因子可能引发神经元发育异常，最终导致食管动力受损。这些数据表明，在相关疾病，如胃食管反流病的发病机制的潜在影响。
As a master component of endosomal sorting complex required for transport proteins, hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs) participates multiple cellular behaviors. However, the physiological role of Hgs in smooth muscle cells (SMCs) is by far unknown. Here we explored the in vivo function of Hgs in SMCs by using a conditional gene knockout strategy. Hgs deficiency in SMCs uniquely led to a progressive dilatation of esophagus with a remarkable thinning muscle layer. Of note, the mutant esophagus showed a decreased contractile responsiveness to potassium chloride and acetylcholine stimulation. Furthermore, an increase in the inhibitory neurites along with an intense infiltration of T lymphocytes in the mucosa and muscle layer were observed. Consistently, Hgs deficiency in SMCs resulted in a disturbed expression of a set of genes involved in neurotrophin and inflammation, suggesting that defective SMC might be a novel source for excessive production of cytokines and chemokines which may trigger the neuronal dysplasia and ultimately contribute to the compromised esophageal motility. The data suggest potential implications in the pathogenesis of related diseases such as gastroesophageal reflux disease.
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DOI：
10.1083/jcb.201301005
发表时间：
2013-04-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Romer AI;Singh J;Rattan S;Krauss RS
通讯作者：
Krauss RS
影响因子：
3.5
作者：
Diem, R;Hobom, M;Bähr, M
通讯作者：
Bähr, M
影响因子：
9.6
作者：
HOLMES, TW
通讯作者：
HOLMES, TW
影响因子：
3.5
作者：
Rodrigues, D. M.;Li, A. Y.;Blennerhassett, M. G.
通讯作者：
Blennerhassett, M. G.
影响因子：
29.4
作者：
Sivarao, DV;Mashimo, HL;Goyal, RK
通讯作者：
Goyal, RK