論文 - 詳細
RRC ID | 34894 |
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著者 | Kelloniemi A, Aro J, Näpänkangas J, Koivisto E, Mustonen E, Ruskoaho H, Rysä J. |
タイトル | TSC-22 up-regulates collagen 3a1 gene expression in the rat heart. |
ジャーナル | BMC Cardiovasc Disord |
Abstract |
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. |
巻・号 | 15 |
ページ | 122 |
公開日 | 2015-10-13 |
DOI | 10.1186/s12872-015-0121-2 |
PII | 10.1186/s12872-015-0121-2 |
PMID | 26464165 |
PMC | PMC4604760 |
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 |
IF | 2.078 |
引用数 | 0 |
WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS |
リソース情報 | |
遺伝子材料 | AxCAmTSC-22 (forward) (RDB02760) AxCALacZ (RDB01745) |