| MicroRNA-21 is a key determinant in IL-11/Stat3 anti-apoptotic signalling pathway in preconditioning of skeletal myoblasts. | |
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MedLine Citation:
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PMID: 20498256 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: We have previously shown that preconditioning of stem and progenitor cells promotes their survival post-engraftment in the infarcted heart. The present study was designed to (i) delineate the role of microRNA-21 (miR-21) in interleukin-11 (IL-11) signalling during preconditioning of skeletal myoblasts (MY) and (ii) study the long-term fate of preconditioned MY ((PC)MY) post-transplantation in the infarcted heart. METHODS AND RESULTS: We report that pharmacological preconditioning of MY with diazoxide showed robust expression of IL-11 and activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and signal transducers and activators of transcription-3 (Stat3) with concomitantly increased miR-21. These molecular events improved cytoprotection of (PC)MY under oxidant stress in vitro which was compromised by pre-treatment of (PC)MY with IL-11-specific siRNA, Erk1/2 blocker, or anti-miR-21. In vivo studies for sry-gene detection in a female rat heart model of acute myocardial infarction showed two-fold higher survival of male donor (PC)MY 4 and 7 days post-engraftment. Long-term fate of the engrafted cells was determined at 4 months after transplantation. Immunohistological studies revealed that in comparison with (non-PC)MY, (PC)MY improved angiogenic response in the heart which was evident from a higher number of blood vessels per surface area (0.155 mm(2)) and myogenic differentiation of (PC)MY in the heart. Indices of myocardial contractility including ejection fraction and fractional shortening showed significant improvement in (PC)MY-treated animals. CONCLUSION: miR-21 is a key regulator of Erk1/2-Stat3 signalling downstream of IL-11 during preconditioning of MY. The therapeutic benefits of (PC)MY were stable and persisted until 4 months of observation. |
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Authors:
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Khawaja Husnain Haider; Niagara Muhammad Idris; Ha Won Kim; Rafeeq P H Ahmed; Jiang Shujia; Muhammad Ashraf |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-24 |
Journal Detail:
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Title: Cardiovascular research Volume: 88 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-10 Completed Date: 2011-01-11 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 168-78 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Cincinnati, Cincinnati, OH 45267-0529, USA. haiderkh@ucmail.uc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* / drug effects Cell Differentiation Cell Survival Cells, Cultured Diazoxide / pharmacology Disease Models, Animal Female Interleukin-11 / metabolism* Male MicroRNAs / metabolism* Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Myoblasts, Skeletal / drug effects, metabolism*, pathology, transplantation Myocardial Contraction Myocardial Infarction / genetics, metabolism*, pathology, physiopathology, surgery Myocytes, Cardiac / drug effects, metabolism*, pathology, transplantation Neovascularization, Physiologic Oxidative Stress RNA Interference Rats Rats, Inbred F344 STAT3 Transcription Factor / metabolism* Sex-Determining Region Y Protein / genetics Signal Transduction* / drug effects Stroke Volume Time Factors Transfection |
| Grant Support | |
ID/Acronym/Agency:
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HL-080686/HL/NHLBI NIH HHS; HL-087246/HL/NHLBI NIH HHS; HL-087288/HL/NHLBI NIH HHS; HL-089535/HL/NHLBI NIH HHS; R37-HL074272/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-11; 0/MicroRNAs; 0/STAT3 Transcription Factor; 0/Sex-Determining Region Y Protein; 0/Stat3 protein, rat; 0/mirn21 microRNA, rat; 364-98-7/Diazoxide; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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