Document Detail


Thyroid hormone-induced cardiac mechano growth factor expression depends on beating activity.
MedLine Citation:
PMID:  20032059     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechano growth factor (MGF), a splice variant of the IGF-I gene, was first discovered in mechanically overloaded skeletal muscle and was shown to play an important role in proliferation of muscle stem cells. Since then, the presence and effects of MGF have been demonstrated in other tissues. MGF has been shown to act neuroprotectively during brain ischemia, and pretreatment with MGF before myocardial infarction improves cardiac function. Because MGF plays a permissive role in exercise-induced skeletal muscle hypertrophy, we hypothesize that MGF is commonly involved in cardiac hypertrophy. To investigate the regulation of MGF expression in heart, mice were treated with thyroid hormone (T(3)) for 12 d to induce physiological cardiac hypertrophy. MGF mRNA expression was specifically increased in midregions of the septum and left ventricular wall. Interestingly, MGF expression strongly correlated with the increased or decreased beating frequency of hyperthyroid and hypothyroid hearts. To further investigate the mechanically dependent induction of MGF, neonatal rat cardiomyocytes were isolated and exposed to T(3). Upon T(3) treatment, cardiomyocytes increased both contractile activity measured as beats per minute and MGF as well as IGF-IEa mRNA expression. Importantly, when cardiomyocytes were contractile arrested by KCl, simultaneous exposure to T(3) prevented the up-regulation of MGF, whereas IGF-IEa was still induced. These studies demonstrated that MGF but not IGF-IEa expression is dependent on beating activity. These findings suggest that MGF is specifically stimulated by mechanical loading of the heart to mediate the hypertrophic response to thyroid hormone.
Authors:
Miriam van Dijk-Ottens; Ingrid H C Vos; Peter W A Cornelissen; Alain de Bruin; Maria E Everts
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Publication Detail:
Type:  Journal Article     Date:  2009-12-23
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-26     Completed Date:  2010-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  830-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.158, NL-3508 TD Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing
Animals
Animals, Newborn
Genetic Variation
Hyperthyroidism / chemically induced,  physiopathology
Hypothyroidism / chemically induced,  physiopathology
Insulin-Like Growth Factor I / genetics*,  pharmacology,  physiology
Mice
Mice, Inbred C57BL
Muscle, Skeletal / drug effects,  physiology
Myocytes, Cardiac / physiology
Physical Conditioning, Animal
Polymerase Chain Reaction
Propylthiouracil / pharmacology
RNA / genetics
RNA, Messenger / genetics
Rats
Rats, Wistar
Thyroid Gland / physiology
Triiodothyronine / pharmacology*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/mechano-growth factor, mouse; 51-52-5/Propylthiouracil; 63231-63-0/RNA; 67763-96-6/Insulin-Like Growth Factor I; 6893-02-3/Triiodothyronine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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