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

Abstract 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.

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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 ◽

10.1186/s13287-020-01940-z ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Guodong Song ◽

Jia Zhou ◽

Ruimei Song ◽

Dalu Liu ◽

Weidi Yu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Long Noncoding Rna ◽

Therapeutic Efficacy ◽

Noncoding Rna ◽

Sodium Taurocholate ◽

High Morbidity

Abstract 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 knockdown 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.

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Resveratrol improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells in rats with severe acute pancreatitis

International Immunopharmacology ◽

10.1016/j.intimp.2019.106128 ◽

2020 ◽

Vol 80 ◽

pp. 106128 ◽

Cited By ~ 2

Author(s):

Dalu Liu ◽

Guodong Song ◽

Zhilong Ma ◽

Xiang Geng ◽

Yuxiang Dai ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Therapeutic Efficacy

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Circular rna zfp644 enahances the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging MIR-21-3P

Cytotherapy ◽

10.1016/s1465324921004977 ◽

2021 ◽

Vol 23 (5) ◽

pp. S136

Author(s):

G. Song

Keyword(s):

Stem Cells ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Therapeutic Efficacy ◽

Circular Rna

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Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells

Bioscience Reports ◽

10.1042/bsr20170347 ◽

2017 ◽

Vol 37 (4) ◽

Cited By ~ 26

Author(s):

Lei Zhang ◽

Xiangyi Sun ◽

Shuo Chen ◽

Chao Yang ◽

Ben Shi ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Mesenchymal Stem Cells ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Chondrogenic Differentiation ◽

Cellular Differentiation ◽

Downstream Target ◽

Mirna Expression Profiling ◽

Multiple Signaling

miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305, which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-β pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305-Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.

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Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells (huMSCs) Carrying MicroRNA-342 Relieve Protect Severe Acute Pancreatitis Injury (SAP)

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2744 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1838-1843

Author(s):

Xiaohong Zhou ◽

Xuzhong Hao ◽

Feifei He

Keyword(s):

Stem Cells ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Severe Acute Pancreatitis ◽

Pancreatic Tissue ◽

Inflammatory Factors ◽

Control Group ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.

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