Quantitative proteomics analysis reveals the pathogenesis of obstructed defecation syndrome caused by abnormal expression of dystrophin  

作　　者：Wen-Zhe Li Yu Xiong Tian-Kun Wang Yan-Yan Chen Song-Lin Wan Lu-Yao Li Meng Xu Jing-Jing Tong Qun Qian Cong-Qing Jiang Wei-Cheng Liu 

机构地区：[1]Department of Colorectal and Anal Surgery(Clinical Center for Pelvic Floor Surgery),Clinical Center of Constipation and Pelvic Floor Disease of Wuhan,Hubei Key Laboratory of Intestinal and Colorectal Diseases,Clinical Center of Intestinal and Colorectal Diseases of Hubei Province,Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei Province,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei Province,China [2]Department of Radiation and Medical Oncology for Esophageal Mediastinal and Lymphatic Tumors,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei Province,China [3]Center for Evidence-Based and Translational Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei Province,China [4]Department of Pathology,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei Province,China [5]School of Life Sciences,Central China Normal University,Wuhan 430071,Hubei Province,China

出　　处：《World Journal of Gastroenterology》2024年第45期4817-4835,共19页世界胃肠病学杂志（英文）

基　　金：Supported by the National Natural Science Foundation of China,No.81500505;the Construction of Predominant Disciplines of Zhongnan Hospital of Wuhan University,No.XKJS202017;the Medical Science and Technology Innovation Platform of Joint Foundation of Health Commission of Hubei Province,Zhongnan Hospital of Wuhan University,No.PTXM2021025;the Hubei Provincial Natural Science Foundation,No.2023AFC013.

摘　　要：BACKGROUND Obstructed defecation syndrome(ODS)represents the most prevalent form of chronic constipation,affecting a diverse patient population,leading to numerous complications,and imposing a significant burden on healthcare resources.Most ODS patients have insufficient rectal propulsion,but the exact mechanism underlying the pathogenesis of ODS remains unclear.AIM To explore the molecular mechanism underlying the pathogenesis of ODS.METHODS A total of 30 pairs of rectal samples were collected from patients with ODS(ODS group)or grade IV prolapsed hemorrhoids without constipation(control group)for quantitative proteomic and bioinformatic analysis.Subsequently,50 pairs of paraffin-embedded rectal specimens were selected for immunohistochemistry and immunofluorescence studies to validate the analysis results.Human intestinal smooth cell contractile function experiments and electrophysiological experiments were conducted to verify the physiological functions of target proteins.Cellular ultrastructure was detected using transmission electron microscopy.RESULTS In comparison to the control group,the expression level of dystrophin(DMD)in rectal specimens from ODS patients was markedly reduced.This finding was corroborated using immunohistochemistry and immunofluorescence techniques.The diminished expression of DMD compromised the contractile function of intestinal smooth muscle cells.At the molecular level,nucleoporin protein 153 and L-type voltage-gated calcium channel were found to be overexpressed in intestinal smooth muscle cells exhibiting downregulated DMD expression.Electrophysiological experiments confirmed an excessive influx of calcium ions into these cells.Moreover,vacuolar-like structures which may be associated with excessive calcium influx were observed in the cells by transmission electron microscopy.CONCLUSION Decreased DMD expression in intestinal smooth muscle may upregulate L-type voltage-gated calcium channel expression,leading to excessive calcium influx which may cause a decrease in rectal propul

关 键 词：Obstructed defecation syndrome DYSTROPHIN Smooth muscle CONTRACTION PROTEOMICS L-type voltage-gated calcium channel 

分 类 号：R57[医药卫生—消化系统]