Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-?B1/p50 gene in rats.

ABSTRACT: Acute pancreatitis (AP) is a common acute abdominal disease, 10-20% of which can evolve into severe AP (SAP) causing significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential of repairing SAP, but the detailed mechanism remains unknown. We demonstrate here that microRNA-9 (miR-9) modified BMSCs (pri-miR-9-BMSCs) can significantly reduce the pancreatic edema, infiltration, hemorrhage, necrosis, the release of amylase and lipase. Meanwhile, decreased local/systemic inflammatory response (TNF-??, IL-1??, IL-6?, HMGB1?, MPO?, CD68?, IL-4?, IL-10?, and TGF-??) and enhanced regeneration of damaged pancreas (Reg4?, PTF1?, and PDX1?) are also promoted. But these effects diminish or disappear after antagonizing miR-9 (TuD). Besides, we find that miR-9 is negatively correlated with AP and miR-9 agomir which can mimic the effects of pri-miR-9-BMSCs and protect injured pancreas. Furthermore, we investigate that BMSCs deliver miR-9 to the injured pancreas or peripheral blood mononuclear cell (PBMC), which can target the NF-?B1/p50 gene and inhibit the NF-?B signaling pathway (p-P65?, NF-?B1/p50?, I?B??, I?B??). Taken together, these results show that miR-9 is a key paracrine factor of BMSCs attenuating SAP targeting the NF-?B1/p50 gene and suppressing the NF-?B signaling pathway.

SUBMITTER: Qian D 

PROVIDER: S-EPMC5428835 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature