Liu Weicheng, Zhang Qiulei, Li Shu, Li Lang, Ding Zhao, Qian Qun, Fan Lifang, Jiang Congqing
Department of Colorectal Surgery, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Key Laboratory of Intestinal & Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan, 430071, People's Republic of China,
Dig Dis Sci. 2015 Aug;60(8):2304-15. doi: 10.1007/s10620-015-3612-1. Epub 2015 Mar 7.
Recent evidence suggests that colonic macrophages and microRNAs play important roles in motor activity in the gastrointestinal tract. However, there are almost no data concerning colonic macrophages and microRNAs in slow transit constipation.
The purpose of this study was to investigate colonic macrophages and microRNA-128 expression in the pathogenesis of slow transit constipation in colon tissues.
Full-thickness colonic specimens from patients undergoing surgery for slow transit constipation, due to refractoriness to other therapeutic interventions (n = 25), were compared to controls (n = 25), and the number of colonic macrophages (as evaluated by specific monoclonal antibodies) was counted. Gene expression analysis of microRNA-128 was performed by microRNA microarray and qRT-PCR. Lastly, bioinformatics analysis, coupled with luciferase reporter assays, was used to investigate the mRNA transcript(s) targeted by microRNA-128.
Compared to controls, 20 of 25 slow transit constipation patients (80 %) had significantly higher numbers of macrophages in colonic specimens, coupled with down-regulation of microRNA-128. Linear regression analyses showed a significant negative correlation between macrophage number and microRNA-128 expression level. Among 83 bioinformatically predicated candidates, mitogen-activated protein kinase 14 (p38α) was validated to be a direct target of microRNA-128 in human intestinal epithelial cells.
This study presents evidence for the negative correlation of macrophage number and microRNA-128 expression, in slow transit constipation patients, representing a possible mechanism of impaired gastrointestinal motility.
最近有证据表明，结肠巨噬细胞和微小RNA在胃肠道运动活动中起重要作用。然而，关于慢传输型便秘患者结肠巨噬细胞和微小RNA的数据几乎没有。
本研究旨在探讨结肠组织中结肠巨噬细胞和微小RNA-128在慢传输型便秘发病机制中的表达情况。
将因对其他治疗干预无效而接受慢传输型便秘手术患者的全层结肠标本（n = 25）与对照组（n = 25）进行比较，计数结肠巨噬细胞数量（通过特异性单克隆抗体评估）。通过微小RNA微阵列和qRT-PCR对微小RNA-128进行基因表达分析。最后，结合生物信息学分析和荧光素酶报告基因检测，研究微小RNA-128靶向的mRNA转录本。
与对照组相比，25例慢传输型便秘患者中有20例（80%）结肠标本中的巨噬细胞数量显著增加，同时微小RNA-128表达下调。线性回归分析显示巨噬细胞数量与微小RNA-128表达水平之间存在显著负相关。在83个经生物信息学预测的候选基因中，丝裂原活化蛋白激酶14（p38α）被证实是人类肠上皮细胞中微小RNA-128的直接靶点。
本研究提供了证据，表明慢传输型便秘患者中巨噬细胞数量与微小RNA-128表达呈负相关，这可能是胃肠动力受损的一种机制。
