TSC-22 up-regulates collagen 3a1 gene expression in the rat heart

BMC Cardiovascular Disorders

Jaana Rysä⁴  Heikki Ruskoaho³  Erja Mustonen²  Elina Koivisto²  Juha Näpänkangas¹  Jani Aro²  Annina Kelloniemi² 

[1] Department of Pathology, Institute of Diagnostics, Oulu University Hospital, University of Oulu, Oulu, Finland;Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland;Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland;School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland

关键词: Myocardial infarction;    Pressure overload;    Heart failure;    Cardiac hypertrophy;   

Others  :  1228279
DOI  :  10.1186/s12872-015-0121-2

 received in 2015-03-02, accepted in 2015-10-01,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Kelloniemi et al.

【 图 表 】

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