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The Relationship Between Colonic Macrophages and MicroRNA-128 in the Pathogenesis of Slow Transit Constipation
Weicheng Liu1, Qiulei Zhang, Shu Li
1Department 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, 89562063@qq.com.
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.
Insights
In slow transit constipation, increased colonic macrophages correlate with decreased microRNA-128. This suggests a potential mechanism involving macrophages and microRNA-128 in impaired gastrointestinal motility.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Colonic macrophages and microRNAs are implicated in gastrointestinal motility.
- Limited data exist on their role in slow transit constipation (STC).
Purpose of the Study:
- To investigate colonic macrophage presence and microRNA-128 expression in STC pathogenesis.
- To explore the relationship between these factors in colon tissue.
Main Methods:
- Compared colonic tissue from STC patients (n=25) and controls (n=25).
- Quantified colonic macrophages using monoclonal antibodies.
- Analyzed microRNA-128 gene expression via microarray and qRT-PCR.
- Utilized bioinformatics and luciferase assays to identify microRNA-128 targets.
Main Results:
- STC patients showed significantly higher macrophage counts (80%) and lower microRNA-128 levels compared to controls.
- A negative correlation was found between macrophage number and microRNA-128 expression.
- Mitogen-activated protein kinase 14 (p38α) was identified as a direct target of microRNA-128.
Conclusions:
- Elevated colonic macrophages and reduced microRNA-128 are linked in STC.
- This interplay may represent a key mechanism contributing to impaired gastrointestinal motility in STC patients.
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