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Sci Rep. 2017 Apr 3;7(1):581. doi: 10.1038/s41598-017-00629-3.

Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats.

Author information

1
Department of General Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, 241001, China.
2
Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
3
Department of Pharmacology and Pharmaceutical Sciences, USC School of Pharmacy, Los Angeles, California, 90089, USA.
4
Intensive Care Unit, Sir Run Run Shaw Hospital, Affiliated to Zhejiang University of Medicine, Hangzhou, Zhejiang, 310058, China.
5
Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China. zs_song@hotmail.com.

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-α↓, IL-1β↓, IL-6↓, HMGB1↓, MPO↓, CD68↓, IL-4↑, IL-10↑, and TGF-β↑) 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-κB1/p50 gene and inhibit the NF-κB signaling pathway (p-P65↓, NF-κB1/p50↓, IκBα↑, IκBβ↑). Taken together, these results show that miR-9 is a key paracrine factor of BMSCs attenuating SAP targeting the NF-κB1/p50 gene and suppressing the NF-κB signaling pathway.

PMID:
28373667
PMCID:
PMC5428835
DOI:
10.1038/s41598-017-00629-3
[Indexed for MEDLINE]
Free PMC Article

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