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

Abstract

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) 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 CC model. Compared to the control group, CC 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 CC and therapeutic targets for its treatment.

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats

“…ere is evidence that miRNAs take part in the pathogenesis of STC [43][44][45]. e results of co-expression network analysis and RNA-seq analysis showed that co-expressed miRNA networks with specific genes and pathways are related to STC [46,47].…”

Cerebrospinal Fluid Extracellular Vesicles with Distinct Properties in Autoimmune Encephalitis and Herpes Simplex Encephalitis

“…Pathways associated with SOCS1, SHIP1, C/EBP-β, and IL13Rα1 signaling cascades might regulate the development CASPR2 encephalitis but not LGI1 encephalitis. miR-128 was reported to participate in the inflammation pathogenesis by regulating the p38α/M-CSF inflammatory signaling pathway [ 54 ]. Thus, p38α/M-CSF inflammatory signaling pathway might fine-tune anti-LGI1- and anti-CASPR2-associated encephalitis.…”

Efficacy and MicroRNA-Gut Microbiota Regulatory Mechanisms of Acupuncture for Severe Chronic Constipation: Study Protocol for a Randomized Controlled Trial

“…MiRNAs, such as miR-let-7f, miR-let-7e, and miR-200a-3p, were reported to be capable of decreasing the current density of NaV1.5 channel in colonic smooth muscle cells and thus increasing the contractile frequency and amplitude of smooth muscle strips via inhibiting the expression of target gene SCN5A ( 24 ). In an animal experiment, miR-128 was found to present significantly elevated expression in the colonic tissue of mice with functional constipation, which inhibited the p38α/M-CSF signaling pathway leading to impaired function of Cajal cells ( 33 ). The imbalance of intestinal microbiota caused by the disorders of miRNA and related regulatory networks is important for the pathogenesis of SCC.…”