Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation  

作　　者：Yi-Chao Zhang Bao-Xiang Chen Xiao-Yu Xie Yan Zhou Qun Qian Cong-Qing Jiang 

机构地区：[1]Department of Colorectal and Anal Surgery of Zhongnan Hospital of Wuhan University, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Hubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Colorectal and Anal Disease Research Center of Medical School (Zhongnan Hospital of Wuhan University), Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei Province

出　　处：《World Journal of Gastroenterology》2020年第7期717-724,共8页世界胃肠病学杂志（英文版）

摘　　要：BACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients.Its incidence rate is 2%-27%.Slow transit constipation(STC)is a common type of chronic functional constipation,accounting for 10.3%-45.5%of such cases.Scholars have performed many studies on the pathogenesis of STC.These studies have indicated that the occurrence of STC may be related to multiple factors,such as dysfunction of the enteric nervous system,interstitial cells of Cajal(ICC)damage,and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX)in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group.The experimental group included 28 patients with severe colonic STC,and the control group included 18 patients with normal colon tissues.Immunohistochemistry(IHC)was used to detect c-Kit,a specific marker of the ICC.Western blot,immunofluorescence,and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17±3.28 vs 28.69±3.53,P<0.05)and that the distribution was abnormal.Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit:0.462±0.099 vs 0.783±0.178,P<0.01;Smad7:0.626±0.058 vs 0.799±0.03,P<0.01)and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868±0.028 vs 0.482±0.032,P<0.01).There was no significant difference in TGF-βbetween the two groups(0.476±0.028 vs 0.511±0.044,P=0.272).Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P<0.05,|R|>0.8)and TGF-β(P<0.05,|R|=0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling proteiBACKGROUND Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients. Its incidence rate is 2%-27%. Slow transit constipation(STC) is a common type of chronic functional constipation, accounting for 10.3%-45.5% of such cases.Scholars have performed many studies on the pathogenesis of STC. These studies have indicated that the occurrence of STC may be related to multiple factors, such as dysfunction of the enteric nervous system, interstitial cells of Cajal(ICC)damage, and changes in neurotransmitters regulating intestinal peristalsis.AIM To investigate the role of Tenascin-X(TNX) in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODS This study included an experimental group and a control group. The experimental group included 28 patients with severe colonic STC, and the control group included 18 patients with normal colon tissues. Immunohistochemistry(IHC) was used to detect c-Kit, a specific marker of the ICC. Western blot,immunofluorescence, and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTS IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients(22.17 ± 3.28 vs 28.69 ± 3.53, P <0.05) and that the distribution was abnormal. Western blot results showed that cKit and Smad7 levels were significantly decreased in the colon of STC patients(c-kit: 0.462 ± 0.099 vs 0.783 ± 0.178, P < 0.01; Smad7: 0.626 ± 0.058 vs 0.799 ± 0.03, P <0.01) and that TNX and Smad2/3 levels were higher in the STC group(TNX:0.868 ± 0.028 vs 0.482 ± 0.032, P < 0.01). There was no significant difference in TGF-β between the two groups(0.476 ± 0.028 vs 0.511 ± 0.044, P = 0.272). Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7(P < 0.05, |R| > 0.8) and TGF-β(P < 0.05, |R| = 0.7).CONCLUSION The extracellular matrix protein TNX may activate the TGF-β

关 键 词：Slow transit constipation TENASCIN-X Extracellular matrix glycoproteins TGF-Β 

分 类 号：R574.62[医药卫生—消化系统]