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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 321; no. 4; pp. G436 - G447
• Main Authors: Hong, Yuntian, Ren, Xianghai, Liu, Weicheng, Sun, Kongliang, Chen, Baoxiang, Liu, Bo, Yu, Xueqiao, Chen, Quanjiao, Qian, Qun, Xie, Xiaoyu, Jiang, Congqing
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.10.2021
• Subjects: Animal models; Cerebrospinal fluid; Colony-stimulating factor; Constipation; Cytokines; Epithelial cells; Gastrointestinal diseases; Inflammation; Interleukin 6; Macrophage colony-stimulating factor; Macrophages; Microenvironments; MicroRNAs; miRNA; Morphine; Pathogenesis; Phosphopyruvate hydratase; Quality of life; Signal transduction; Stem cell factor; Stem cells; Therapeutic targets; Tumor necrosis factor-α
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00114.2021

In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation. Chronic constipation (CC) 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 CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was 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 CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture 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 CC and therapeutic targets for its treatment. NEW & NOTEWORTHY In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.