Kelloniemi Annina, Aro Jani, Näpänkangas Juha, Koivisto Elina, Mustonen Erja, Ruskoaho Heikki, Rysä Jaana
Research Unit of Biomedicine (Pharmacology & Toxicology), University of Oulu, Oulu, Finland.
Department of Pathology, Institute of Diagnostics, Oulu University Hospital, University of Oulu, Oulu, Finland.
BMC Cardiovasc Disord. 2015 Oct 13;15:122. doi: 10.1186/s12872-015-0121-2.
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.
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.
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.
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.
转化生长因子（TGF）-β是心肌梗死（MI）后发生的心脏重塑以及高血压性心脏病中的关键介质之一。TGF-β刺激克隆22（TSC-22）是一种在许多组织中表达且具有多种转录调节活性的亮氨酸拉链蛋白。然而，其在心脏中的功能尚不清楚。
本研究的目的是在体内心脏重塑过程以及体外心肌细胞中表征心脏TSC-22的表达。此外，我们使用TSC-22基因转移来研究TSC-22对心脏基因表达和功能的影响。
我们发现TSC-22会被多种肥大刺激迅速上调，在MI后重塑过程中，TSC-22的mRNA和蛋白水平在第1天就已上调（分别为4.1倍，P<0.001和3.0倍，P<0.05）。我们观察到氯沙坦和美托洛尔治疗均降低了左心室TSC-22基因的表达。最后，通过局部心肌内腺病毒介导的基因传递使TSC-22过表达表明，TSC-22似乎在调节心脏中III型胶原α1基因的表达中发挥作用。
这些结果表明，TSC-22的表达是对心脏负荷增加的一种反应。此外，我们的数据表明，通过在体内调节心脏中的胶原蛋白表达，TSC-22可能成为预防纤维化治疗的潜在靶点。
