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 de...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00629-3 |
| _version_ | 1818991374679146496 |
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| author | Daohai Qian Ge Wei Chenglei Xu Zhigang He Jie Hua Jian Li Qili Hu Shengping Lin Jian Gong Hongbo Meng Bo Zhou Hongfei Teng Zhenshun Song |
| author_facet | Daohai Qian Ge Wei Chenglei Xu Zhigang He Jie Hua Jian Li Qili Hu Shengping Lin Jian Gong Hongbo Meng Bo Zhou Hongfei Teng Zhenshun Song |
| author_sort | Daohai Qian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T20:09:15Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:09:15Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bfb8527fd5b047f3b1734961b5c705dc2022-12-21T19:27:51ZengNature PortfolioScientific Reports2045-23222017-04-017111710.1038/s41598-017-00629-3Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in ratsDaohai Qian0Ge Wei1Chenglei Xu2Zhigang He3Jie Hua4Jian Li5Qili Hu6Shengping Lin7Jian Gong8Hongbo Meng9Bo Zhou10Hongfei Teng11Zhenshun Song12Department of General Surgery, Yijishan Hospital, Wannan Medical CollegeDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineIntensive Care Unit, Sir Run Run Shaw Hospital, Affiliated to Zhejiang University of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineDepartment of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-017-00629-3 |
| spellingShingle | Daohai Qian Ge Wei Chenglei Xu Zhigang He Jie Hua Jian Li Qili Hu Shengping Lin Jian Gong Hongbo Meng Bo Zhou Hongfei Teng Zhenshun Song Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats Scientific Reports |
| 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 |
| title_full | Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats |
| title_fullStr | Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats |
| title_full_unstemmed | Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats |
| title_short | Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats |
| title_sort | bone marrow derived mesenchymal stem cells bmscs repair acute necrotized pancreatitis by secreting microrna 9 to target the nf κb1 p50 gene in rats |
| url | https://doi.org/10.1038/s41598-017-00629-3 |
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