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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Autores principales: 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
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:bfb8527fd5b047f3b1734961b5c705dc2021-12-02T15:05:13ZBone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats10.1038/s41598-017-00629-32045-2322https://doaj.org/article/bfb8527fd5b047f3b1734961b5c705dc2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00629-3https://doaj.org/toc/2045-2322Abstract 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.Daohai QianGe WeiChenglei XuZhigang HeJie HuaJian LiQili HuShengping LinJian GongHongbo MengBo ZhouHongfei TengZhenshun SongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
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
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_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_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_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
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/bfb8527fd5b047f3b1734961b5c705dc
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