Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

Stem Cell Research & Therapy

Hongbo Meng¹  Dalu Liu¹  Ruimei Song¹  Wangcheng Xie¹  Jian Gong¹  Tingsong Yang¹  Guodong Song¹  Zhenshun Song¹  Weidi Yu¹  Jia Zhou²  Zhilong Ma³ 

[1] Department of General Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of Medicine, 200072, Shanghai, China;Department of General Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of Medicine, 200072, Shanghai, China;Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 200336, Shanghai, China;Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 200336, Shanghai, China;

关键词: Long noncoding RNA H19;    Mesenchymal stem cells;    Severe acute pancreatitis;    Autophagy;    Cell proliferation;   

DOI  :  10.1186/s13287-020-01940-z

来源: Springer

【 摘 要 】

BackgroundPatients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP.MethodsMSCs transfected with LncRNA H19 overexpression and knockdown plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP.ResultsOverexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation.ConclusionsIn conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

【 授权许可】

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