Research Paper

miR-128 participates in the pathogenesis of slow transit constipation by regulating the p38α/M-CSF inflammatory signaling pathway

Yuntian Hong^1,^2,³, Weicheng Liu^1,^2,^3,^4,⁵, Bo Liu^1,^2,³, Xianghai Ren^1,^2,^3,^4,⁵, Kongliang Sun^1,^2,³, Xueqiao Yu^1,^2,^3,^4,⁵, Quanjiao Chen⁶, Qun Qian^1,^2,^3,^4,⁵, Xiaoyu Xie^1,^2,^3,^4,⁵, Congqing Jiang^1,^2,^3,^4,⁵

¹Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
²Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan 430071, China
³Hubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Wuhan 430071, China
⁴Colorectal and Anal Disease Research Center of Medical School (Zhongnan Hospital of Wuhan University), Wuhan 430071, China
⁵Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei Province, Wuhan 430071, China
⁶CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, CAS Center for Influenza Research and Early Warning, Chinese Academy of Sciences, Wuhan 430071, China

* Equal contribution

Received: September 25, 2020Accepted: January 14, 2021

https://doi.org/10.18632/aging.

Copyright: © 2021 Hong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Slow transit constipation (STC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in STC. Here, we successfully constructed a murine model of STC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) were low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in STC model. Compared to the control group, STC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony stimulating factors (M-CSF). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, co-culture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of STC and therapeutic targets for its treatment.