MicroRNA-141 ameliorates alcoholic hepatitis‑induced intestinal injury and intestinal endotoxemia partially via a TLR4-dependent mechanism.Int J Mol Med. 2019 Aug; 44(2):569-581.IJ
Alcoholic hepatitis (AH) is a fatal inflammatory syndrome with no effective treatments. Intestinal injury and intestinal endotoxemia (IETM) contribute greatly in the development of AH. MicroRNAs (miRNAs/miRs) have been reported to affect intestinal injury. The present study aims to investigate the role of miR‑141 in intestinal injury and IETM of AH. An AH model was successfully established in mice and they were the injected with a series of miR‑141 mimic, miR‑141 inhibitor or toll like receptor 4 monoclonal antibody (TLR4mAb; an inhibitor of the Toll‑like receptor TLR pathway). After that, the intestinal tissues and intestinal epithelial cells were isolated from differently treated AH mice. The expression of miR‑141 and TLR pathway‑associated genes and the levels of inflammatory factors were determined. Furthermore, a target prediction program and a luciferase reporter assay were employed to examine whether miR‑141 targets TLR4. Finally, MTT and transwell assays were carried out to detect cell viability and cell permeability. Intestinal tissues from AH mice treated with miR‑141 mimic or TLR4mAb exhibited lower levels of inflammatory factors and reduced expression of the TLR pathway‑associated genes, suggesting a decreased inflammatory response as well as inactivation of the TLR pathway by miR‑141. The luciferase reporter assay suggested that miR‑141 negatively regulated TLR4. Intestinal epithelial cells treated with miR‑141 mimic or TLR4mAb demonstrated enhanced viability and reduced permeability. Opposite results were observed in AH mice treated with a miR‑141 inhibitor. Collectively, the results of the present study demonstrated that miR‑141 could ameliorate intestinal injury and repress the progression of IETM through targeting TLR4 and inhibiting the TLR pathway.