Overexpression of microRNA-126 in Adipose-Derived Mesenchymal Stem Cells Alleviate the Alcoholic Liver Injury

Abstract

Alcoholic liver disease (ALD) is a major global health issue. This study explores the therapeutic efficacy of microRNA-126 (miR-126)-engineered adipose-derived mesenchymal stem cells (ADMSCs) in ALD, particularly focusing on their impact on the intestinal barrier. Male mice was used to establish an ALD model. Subsequently, both unmodified and miR-126-engineered ADMSCs were transplanted into these ALD models. A variety of techniques were then employed to assess liver injury, the integrity of the intestinal epithelial barrier (IEB), and the gut vascular barrier (GVB) across different intervention groups. ADMSCs effectively mitigated liver injury in the ALD model, as evidenced by improving liver function (serum ALT and AST levels) and injury, and reversing the serum LPS translocation. Furthermore, miR-126-overexpressing engineered ADMSCs demonstrated the most potent effects compared to other groups. ALD-induced damage to the intestinal epithelium and vascular barriers was not only ameliorated by ADMSCs but also further enhanced by ADMSCs^miR−126(+) treatment. Additionally, the expression levels of PV-1 (a positive marker for GVB injury) and ZO-1 (a negative marker for IEB injury) were most markedly reduced and elevated following treatment with ADMSCs^miR−126(+), respectively. Further analyses revealed that ADMSCs treatment actives PI3K/Akt/eNOS pathway and subsequently repressing the expression of caspase-3, thereby repairing IEB and GVB, in which miR-126 can improve the above effect. ADMSCs can alleviate ALD by regulating the IEB and GVB, and miR-126-engineered ADMSCs offer enhanced therapeutic benefits. These findings unveil a novel therapeutic mechanism for ALD that involves protection against damage to the IEB and GVB.