MiR-141-Modified Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits the Progression of Severe Acute Pancreatitis

Abstract

The therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on severe acute pancreatitis (SAP) and miRNAs are currently the research hotspots. This study intends to explore the potential impact of miR-141-modified BMSCs on SAP. After establishment of rat model of SAP, the animals were grouped into control group, model group, BMSCs group, miR-141 group, positive control group, and PI3K/mTOR signaling agonist group (agonist group) followed by analysis of miR-141 expression by RT-qPCR and the expression of serum amylase, IL-6, TNF-α, TAP, PI3K, mTOR, and LC3-II by Western blot and ELISA. miR-141 was significantly up-regulated in the miR-141-modified BMSCs group (p > 0.05). The contents of serum amylase, IL-6, TNF-α, and TAP was increased in SAP rats and decreased after BMSC treatment (p > 0.05). The increased autophagy flux in the rats with SAT was reduced upon treatment with BMSCs and autophagy flux was decreased in miR-141 group but increased in positive control group. The model and positive control group presented highest expression of LC3-II, p-PI3K and p-mTOR, followed by BMSCs group and miR-141 group (p < 0.05). In conclusion, miR-141-modified BMSCs decrease the phosphorylation of PI3K and mTOR to inhibit PI3K/mTOR signaling activity and downregulate LC3-II protein to inhibit autophagy, thereby ameliorating the development of SAP, indicating that miR-141 might be a therapeutic target for SAP.