Document Detail


MicroRNA-21 is a key determinant in IL-11/Stat3 anti-apoptotic signalling pathway in preconditioning of skeletal myoblasts.
MedLine Citation:
PMID:  20498256     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Khawaja Husnain Haider; Niagara Muhammad Idris; Ha Won Kim; Rafeeq P H Ahmed; Jiang Shujia; Muhammad Ashraf
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-24
Journal Detail:
Title:  Cardiovascular research     Volume:  88     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-10     Completed Date:  2011-01-11     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  168-78     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Cincinnati, Cincinnati, OH 45267-0529, USA. haiderkh@ucmail.uc.edu
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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