The Relationship Between Colonic Macrophages and MicroRNA-128 in the Pathogenesis of Slow Transit Constipation

Abstract

Background: 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.

Aim: The purpose of this study was to investigate colonic macrophages and microRNA-128 expression in the pathogenesis of slow transit constipation in colon tissues.

Methods: 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.

Results: 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.

Conclusions: 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.