Bone marrow-derived mesenchymal stem cells attenuate severe acute pancreatitis via regulation of microRNA-9 to inhibit necroptosis in rats

Zhou

et al. 2020

Preprint

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Background: Patients 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.Methods: MSCs transfected with LncRNA H19 overexpression and knock down plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP.Results: Overexpressing 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.Conclusions: In 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.

Section: Introductionmentioning

confidence: 71%

Section: Cell Culturementioning

confidence: 99%

Section: In Vivo Protocolmentioning

confidence: 99%

Section: Histopathologic Examinationmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

See 3 more Smart Citations

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

Zhou

et al. 2020

Preprint

Self Cite

Journal Cellular Physiology

MicroRNAs in acute pancreatitis: From pathogenesis to novel diagnosis and therapy

Yang

Huang

Luo

et al. 2019

Acute pancreatitis (AP) is an inflammatory disorder initiated by activation of pancreatic zymogens, leading to pancreatic injury and systemic inflammatory response. MicroRNAs (miRNAs) have emerged as important regulators of gene expression and key players in human physiological and pathological processes. Discoveries over the past decade have confirmed that altered expression of miRNAs is implicated in the pathogenesis of AP. Indeed, a number of miRNAs have been found to be dysregulated in various cell types involved in AP such as acinar cells, macrophages, and lymphocytes. These aberrant miRNAs can regulate acinar cell necrosis and apoptosis, local and systemic inflammatory response, thereby contributing to the initiation and progression of AP. Moreover, patients with AP possess unique miRNA signatures when compared with healthy individuals or those with other diseases. In view of their stability and easy detection, therefore, miRNAs have the potential to act as biomarkers for the diagnosis and assessment of patients with AP. In this review, we provide an overview of the novel cellular and molecular mechanisms underlying the roles of miRNAs during the disease processes of AP, as well as the potential diagnosis and therapeutic biomarkers of miRNAs in patients with AP.

Medicinal Research Reviews

Mesenchymal stromal cell therapy for pancreatitis: Progress and challenges

Zhou

Yang

et al. 2021

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Pancreatitis is a common gastrointestinal disease with no effective therapeutic options, particularly for cases of severe acute and chronic pancreatitis (CP). Mesenchymal stromal cells (MSCs) are multipotent cells with diverse biological properties, including directional migration, paracrine, immunosuppressive, and antiinflammatory effects, which are considered an ideal candidate cell type for repairing tissue damage caused by various pathogenies. Several researchers have reported significant therapeutic efficacy of MSCs in animal models of acute and CP. However, the specific underlying mechanisms are yet to be clarified and clinical application of MSCs as pancreatitis therapy has rarely been reported. This review mainly focuses on the potential and challenges in clinical application of MSCs for treatment of acute and CP, along with discussion of the underlying molecular mechanisms.