Reference - Detail
|Author||Kelloniemi A, Aro J, Näpänkangas J, Koivisto E, Mustonen E, Ruskoaho H, Rysä J.|
|Title||TSC-22 up-regulates collagen 3a1 gene expression in the rat heart.|
|Journal||BMC Cardiovasc Disord|
BACKGROUND:The transforming growth factor (TGF)-β is one of the key mediators in cardiac remodelling occurring after myocardial infarction (MI) and in hypertensive heart disease. The TGF-β-stimulated clone 22 (TSC-22) is a leucine zipper protein expressed in many tissues and possessing various transcription-modulating activities. However, its function in the heart remains unknown.
METHODS:The aim of the present study was to characterize cardiac TSC-22 expression in vivo in cardiac remodelling and in myocytes in vitro. In addition, we used TSC-22 gene transfer in order to examine the effects of TSC-22 on cardiac gene expression and function.
RESULTS:We found that TSC-22 is rapidly up-regulated by multiple hypertrophic stimuli, and in post-MI remodelling both TSC-22 mRNA and protein levels were up-regulated (4.1-fold, P <0.001 and 3.0-fold, P <0.05, respectively) already on day 1. We observed that both losartan and metoprolol treatments reduced left ventricular TSC-22 gene expression. Finally, TSC-22 overexpression by local intramyocardial adenovirus-mediated gene delivery showed that TSC-22 appears to have a role in regulating collagen type IIIα1 gene expression in the heart.
CONCLUSIONS:These results demonstrate that TSC-22 expression is induced in response to cardiac overload. Moreover, our data suggests that, by regulating collagen expression in the heart in vivo, TSC-22 could be a potential target for fibrosis-preventing therapies.
|MeSH||Animals Antihypertensive Agents / therapeutic use Cells, Cultured Collagen Type III / genetics* Female Gene Expression Gene Transfer Techniques Heart Failure / drug therapy Heart Failure / metabolism Hypertension / metabolism* Losartan / therapeutic use Male Metoprolol / therapeutic use Muscle Cells / metabolism Myocardial Infarction / metabolism* Myocardium / metabolism* RNA, Messenger / metabolism Rats, Inbred SHR Rats, Inbred WKY Rats, Sprague-Dawley Repressor Proteins / metabolism* Signal Transduction Up-Regulation* Ventricular Remodeling|
|WOS Category||CARDIAC & CARDIOVASCULAR SYSTEMS|
|DNA material||AxCAmTSC-22 (forward) (RDB02760) AxCALacZ (RDB01745)|