title: Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/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-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.
authors.affiliation: Department of General Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, 241001, China.|Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.|Department of Pharmacology and Pharmaceutical Sciences, USC School of Pharmacy, Los Angeles, California, 90089, USA.
authors.forename: Daohai
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Chenglei
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hua
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Qili
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Intensive Care Unit, Sir Run Run Shaw Hospital, Affiliated to Zhejiang University of Medicine, Hangzhou, Zhejiang, 310058, China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, China. zs_song@hotmail.com.
authors.forename: Zhenshun
authors.initials: Z
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: C582333:MIRN9 microRNA, rat; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit