BMC Cardiovascular Disorders | |
TSC-22 up-regulates collagen 3a1 gene expression in the rat heart | |
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.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20151014011608639.pdf | 957KB | download | |
Fig. 6. | 77KB | Image | download |
Fig. 5. | 32KB | Image | download |
Fig. 4. | 66KB | Image | download |
Fig. 3. | 32KB | Image | download |
Fig. 2. | 46KB | Image | download |
Fig. 1. | 40KB | Image | download |
【 图 表 】
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
【 参考文献 】
- [1]Mann DL, Barger PM, Burkhoff D: Myocardial recovery and the failing heart: myth, magic, or molecular target? J Am Coll Cardiol 2012, 60:2465-72.
- [2]Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al.: Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation 2014, 129:e28-292.
- [3]Oka T, Xu J, Molkentin JD: Re-employment of developmental transcription factors in adult heart disease. Semin Cell Dev Biol 2007, 18:117-31.
- [4]Rose BA, Force T, Wang Y: Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev 2010, 90:1507-46.
- [5]Akazawa H, Komuro I: Roles of cardiac transcription factors in cardiac hypertrophy. Circ Res 2003, 92:1079-88.
- [6]Dobaczewski M, Chen W, Frangogiannis NG: Transforming growth factor (TGF)-beta signaling in cardiac remodeling. J Mol Cell Cardiol 2011, 51:600-6.
- [7]Bujak M, Frangogiannis NG: The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res 2007, 74:184-95.
- [8]Rosenkranz S: TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 2004, 63:423-32.
- [9]Liu G, Ding W, Neiman J, Mulder KM: Requirement of Smad3 and CREB-1 in mediating transforming growth factor-beta (TGF beta) induction of TGF beta 3 secretion. J Biol Chem 2006, 281:29479-90.
- [10]Shibanuma M, Kuroki T, Nose K: Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors. J Biol Chem 1992, 267:10219-24.
- [11]Kester HA, Blanchetot C, Hertog J, Van der Saag PT, Van der Burg B: Transforming growth factor- beta -stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J Biol Chem 1999, 274:27439-47.
- [12]Choi SJ, Moon JH, Ahn YW, Ahn JH, Kim DU, Han TH: Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation. Mol Cell Biochem 2005, 271:23-8.
- [13]Yan X: TSC-22 promotes transforming growth factor beta-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity. Mol Cell Biol 2011, 31:3700-9.
- [14]Dobens LL, Hsu T, Twombly V, Gelbart WM, Raftery LA, Kafatos FC: The Drosophila bunched gene is a homologue of the growth factor stimulated mammalian TSC-22 sequence and is required during oogenesis. Mech Dev 1997, 65:197-208.
- [15]Kawamata H, Nakashiro K, Uchida D, Hino S, Omotehara F, Yoshida H, et al.: Induction of TSC-22 by treatment with a new anti-cancer drug, vesnarinone, in a human salivary gland cancer cell. Br J Cancer 1998, 77:71-8.
- [16]Kawamata H, Fujimori T, Imai Y: TSC-22 (TGF-beta stimulated clone-22): a novel molecular target for differentiation-inducing therapy in salivary gland cancer. Curr Cancer Drug Targets 2004, 4:521-9.
- [17]Ohta S, Yanagihara K, Nagata K: Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor beta. Biochem J 1997, 324(Pt 3):777-82.
- [18]Shostak KO, Dmitrenko VV, Vudmaska MI, Naidenov VG, Beletskii AV, Malisheva TA, et al.: Patterns of expression of TSC-22 protein in astrocytic gliomas. Exp Oncol 2005, 27:314-8.
- [19]Iida M, Anna CH, Gaskin ND, Walker NJ, Devereux TR: The putative tumor suppressor Tsc-22 is downregulated early in chemically induced hepatocarcinogenesis and may be a suppressor of Gadd45b. Toxicol Sci 2007, 99:43-50.
- [20]Yu J, Ershler M, Yu L, Wei M, Hackanson B, Yokohama A, et al.: TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia. Blood 2009, 113:5558-67.
- [21]Yoon CH, Rho SB, Kim ST, Kho S, Park J, Jang IS, et al.: Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. PLoS One 2012, 7:e42006.
- [22]Hashiguchi A, Okabayashi K, Asashima M: Role of TSC-22 during early embryogenesis in Xenopus laevis. Dev Growth Differ 2004, 46:535-44.
- [23]Jager J, Greiner V, Strzoda D, Seibert O, Niopek K, Sijmonsma TP, et al.: Hepatic transforming growth factor-beta 1 stimulated clone-22 D1 controls systemic cholesterol metabolism. Mol Metab 2014, 3:155-66.
- [24]Dohrmann CE, Noramly S, Raftery LA, Morgan BA: Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather tract. Dev Dyn 2002, 223:85-95.
- [25]Rysa J, Aro J, Ruskoaho H: Early left ventricular gene expression profile in response to increase in blood pressure. Blood Press 2006, 15:375-83.
- [26]Stanton LW, Garrard LJ, Damm D, Garrick BL, Lam A, Kapoun AM, et al.: Altered patterns of gene expression in response to myocardial infarction. Circ Res 2000, 86:939-45.
- [27]Prussak CE, Almazan MT, Tseng BY: Peptide production from proteins separated by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. Anal Biochem 1989, 178:233-8.
- [28]Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, et al.: Myocardial infarct size and ventricular function in rats. Circ Res 1979, 44:503-12.
- [29]Tenhunen O, Soini Y, Ilves M, Rysa J, Tuukkanen J, Serpi R, et al.: p38 Kinase rescues failing myocardium after myocardial infarction: evidence for angiogenic and anti-apoptotic mechanisms. FASEB J 2006, 20:1907-9.
- [30]Wang Y, Huang S, Sah VP, Ross J Jr, Brown JH, Han J, et al.: Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J Biol Chem 1998, 273:2161-8.
- [31]Niwa H, Yamamura K, Miyazaki J: Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 1991, 108:193-9.
- [32]Tenhunen O, Rysa J, Ilves M, Soini Y, Ruskoaho H, Leskinen H: Identification of cell cycle regulatory and inflammatory genes as predominant targets of p38 mitogen-activated protein kinase in the heart. Circ Res 2006, 99:485-93.
- [33]Rysa J, Leskinen H, Ilves M, Ruskoaho H: Distinct upregulation of extracellular matrix genes in transition from hypertrophy to hypertensive heart failure. Hypertension 2005, 45:927-33.
- [34]Ronkainen VP, Ronkainen JJ, Hanninen SL, Leskinen H, Ruas JL, Pereira T, et al.: Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. FASEB J 2007, 21:1821-30.
- [35]Aro J, Tokola H, Ronkainen VP, Koivisto E, Tenhunen O, Ilves M, et al.: Regulation of cardiac melusin gene expression by hypertrophic stimuli in the rat. Acta Physiol (Oxf) 2013, 207:470-84.
- [36]Koivisto E, Karkkola L, Majalahti T, Aro J, Tokola H, Kerkela R, et al.: M-CAT element mediates mechanical stretch-activated transcription of B-type natriuretic peptide via ERK activation. Can J Physiol Pharmacol 2011, 89:539-50.
- [37]Luosujarvi H, Aro J, Tokola H, Leskinen H, Tenhunen O, Skoumal R, et al.: A novel p38 MAPK target dyxin is rapidly induced by mechanical load in the heart. Blood Press 2010, 19:54-63.
- [38]Mustonen E, Leskinen H, Aro J, Luodonpää M, Vuolteenaho O, Ruskoaho H, et al.: Metoprolol treatment lowers thrombospondin-4 expression in rats with myocardial infarction and left ventricular hypertrophy. Basic Clin Pharmacol Toxicol 2010, 107:709-17.
- [39]Hoshijima M, Chien KR: Mixed signals in heart failure: cancer rules. J Clin Invest 2002, 109:849-55.
- [40]Brand T, Schneider MD: The TGF beta superfamily in myocardium: ligands, receptors, transduction, and function. J Mol Cell Cardiol 1995, 27:5-18.
- [41]Rosenkranz S, Flesch M, Amann K, Haeuseler C, Kilter H, Seeland U, et al.: Alterations of beta-adrenergic signaling and cardiac hypertrophy in transgenic mice overexpressing TGF-beta(1). Am J Physiol Circ Physiol 2002, 283:H1253-62.
- [42]Schultz Jel J, Witt SA, Glascock BJ, Nieman ML, Reiser PJ, Nix SL, et al.: TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J Clin Invest 2002, 109:787-96.
- [43]Schluter KD, Frischkopf K, Flesch M, Rosenkranz S, Taimor G, Piper HM: Central role for ornithine decarboxylase in beta-adrenoceptor mediated hypertrophy. Cardiovasc Res 2000, 45:410-7.
- [44]Schluter KD, Zhou XJ, Piper HM: Induction of hypertrophic responsiveness to isoproterenol by TGF-beta in adult rat cardiomyocytes. Am J Physiol 1995, 269(5 Pt 1):C1311-6.
- [45]Huntgeburth M, Tiemann K, Shahverdyan R, Schluter KD, Schreckenberg R, Gross ML, et al.: Transforming growth factor beta(1) oppositely regulates the hypertrophic and contractile response to beta-adrenergic stimulation in the heart. PLoS One 2011, 6:e26628.
- [46]Brouri F, Hanoun N, Mediani O, Saurini F, Hamon M, Vanhoutte PM, et al.: Blockade of β1- and desensitization of β 2-adrenoceptors reduce isoprenaline-induced cardiac fibrosis. Eur J Pharmacol 2004, 485:227-34.
- [47]De Carvalho FC, Sun Y, Weber KT: Angiotensin II receptor blockade and myocardial fibrosis of the infarcted rat heart. J Lab Clin Med 1997, 129:439-46.
- [48]Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, et al.: Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation 1994, 89:2273-82.
- [49]Boluyt MO, Robinson KG, Meredith AL, Sen S, Lakatta EG, Crow MT, et al.: Heart failure after long-term supravalvular aortic constriction in rats. Am J Hypertens 2005, 18(2 Pt 1):202-12.
- [50]Kuoppala A, Shiota N, Lindstedt KA, Rysä J, Leskinen HK, Luodonpää M, et al.: Expression of bradykinin receptors in the left ventricles of rats with pressure overload hypertrophy and heart failure. J Hypertens 2003, 21:1729-36.
- [51]Kato M, Wang L, Putta S, Wang M, Yuan H, Sun G, et al.: Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells. J Biol Chem 2010, 285:34004-15.
- [52]Jane-Lise S, Corda S, Chassagne C, Rappaport L: The extracellular matrix and the cytoskeleton in heart hypertrophy and failure. Heart Fail Rev 2000, 5:239-50.
- [53]Hino S, Kawamata H, Uchida D, Omotehara F, Miwa Y, Begum NM, et al.: Nuclear translocation of TSC-22 (TGF-beta-stimulated clone-22) concomitant with apoptosis: TSC-22 as a putative transcriptional regulator. Biochem Biophys Res Commun 2000, 278:659-64.