The basic helix-loop-helix transcription factor scleraxis regulates fibroblast collagen synthesis.

Abstract:

:The transcription factor scleraxis has been implicated in regulating the development of collagen-rich tissues such as tendons and cardiac valves, but its role in general collagen synthesis in the heart is unknown. Scleraxis expression in cardiac fibroblasts was examined, and its ability to regulate gene expression of collagen I alpha 2, the predominant cardiac collagen isoform, was assayed. Using real-time PCR, we demonstrate here that scleraxis mRNA is up-regulated by the profibrotic agonist TGF-beta(1) in rat cardiac myofibroblasts, and that phenoconversion of fibroblasts to myofibroblasts similarly increases scleraxis expression. Over-expression of scleraxis in NIH-3T3 or primary rat cardiac fibroblasts by adenoviral gene delivery is sufficient to significantly increase collagen I alpha 2 gene expression. Using luciferase reporter assays, we demonstrate that scleraxis transactivates the human collagen I alpha 2 promoter in a DNA- and protein-binding dependent manner. Intriguingly, examination of infarcted rat hearts reveals a nearly four-fold increase in scleraxis expression in the infarct scar, but not in non-infarcted tissue. These data support a novel and previously unknown role for scleraxis in the regulation of collagen gene expression in the heart, including in post-infarct scar formation.

journal_name

J Mol Cell Cardiol

authors

Espira L,Lamoureux L,Jones SC,Gerard RD,Dixon IM,Czubryt MP

doi

10.1016/j.yjmcc.2009.03.024

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

188-95

issue

2

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(09)00150-3

journal_volume

47

pub_type

杂志文章
  • Acetaldehyde dehydrogenase 2 deficiency exacerbates cardiac fibrosis by promoting mobilization and homing of bone marrow fibroblast progenitor cells.

    abstract::Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to inv...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.10.006

    authors: Li X,Weng X,Shi H,Gao R,Wang P,Jia D,Zhang S,Dong Z,Sun X,Yang J,Wang Z,Liu R,Li Y,Qiu Z,Hu K,Sun A,Ge J

    更新日期:2019-12-01 00:00:00

  • IL-1beta and TNF-alpha upregulate angiotensin II type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart.

    abstract::Angiotensin (Ang) II plays an important role in post-myocardial infarction (MI) cardiac remodeling. The Ang II type 1 (AT(1)) receptor which mediates most Ang II effects is upregulated on non-myocytes in the post-MI heart. We have shown that pro-inflammatory cytokines increase AT(1) receptor density on cardiac fibrobl...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2004.12.015

    authors: Gurantz D,Cowling RT,Varki N,Frikovsky E,Moore CD,Greenberg BH

    更新日期:2005-03-01 00:00:00

  • Regulation of sodium-calcium exchange and mitochondrial energetics by Bcl-2 in the heart of transgenic mice.

    abstract::Our previous work in cultured cells has shown that the maintenance of mitochondrial Ca(2+) homeostasis is essential for cell survival, and that the anti-apoptotic protein Bcl-2 is able to maintain a threshold level of mitochondrial Ca(2+) by the inhibition of permeability transition. To test whether Bcl-2 also affects...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1476

    authors: Zhu L,Yu Y,Chua BH,Ho YS,Kuo TH

    更新日期:2001-12-01 00:00:00

  • Inhibition of PI3Kinase-α is pro-arrhythmic and associated with enhanced late Na+ current, contractility, and Ca2+ release in murine hearts.

    abstract:BACKGROUND:Phosphoinositide 3-kinase α (PI3Kα) is a proto-oncogene with high activity in the heart. BYL719 (BYL) is a PI3Kα-selective small molecule inhibitor and a prospective drug for advanced solid tumors. We investigated whether acute pharmacological inhibition of PI3Kα has pro-arrhythmic effects. METHODS & RESULT...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.05.008

    authors: Zhabyeyev P,McLean B,Chen X,Vanhaesebroeck B,Oudit GY

    更新日期:2019-07-01 00:00:00

  • Multiply attenuated, self-inactivating lentiviral vectors efficiently transduce human coronary artery cells in vitro and rat arteries in vivo.

    abstract::Endothelial cells (ECs) in normal vessels are poorly transducible by retroviral vectors, which require cell division for gene transduction. Among retroviruses, lentiviruses have the unique ability to integrate their genome into the chromatin of nondividing cells. Here we show that multiply attenuated, self-inactivatin...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2004.11.031

    authors: Céfaï D,Simeoni E,Ludunge KM,Driscoll R,von Segesser LK,Kappenberger L,Vassalli G

    更新日期:2005-02-01 00:00:00

  • The external work-pressure time integral relationships and the afterload dependence of Frank-Starling mechanism.

    abstract::The mechanisms underlying the Frank-Starling Law of the heart are elusive and the prevalent notion suggests that it is afterload independent. However, isolated fiber studies reveal that the afterload determines cardiac function through cross-bridge dependent mechanisms. The study explores the roles of the afterload, i...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2009.05.007

    authors: Sela G,Landesberg A

    更新日期:2009-10-01 00:00:00

  • β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway.

    abstract::Cardiac β-adrenergic receptors (β-AR) and Ca2+-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca2+ signaling. Elevated diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activati...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2017.04.005

    authors: Pereira L,Bare DJ,Galice S,Shannon TR,Bers DM

    更新日期:2017-07-01 00:00:00

  • Synthesis of leukotrienes by freshly harvested endothelial cells.

    abstract::Endothelial cells produce endothelin, a powerful vasoconstrictor. We report the release of additional vasoconstrictor material in conditional filtrate from freshly harvested cells, which we identified as leukotrienes by radioimmunoassay (RIA) and by high pressure liquid chromatography (HPLC). The material was collecte...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1077

    authors: Kähler J,Conforto A,Dudek R,Termin A,Bing RJ

    更新日期:1993-06-01 00:00:00

  • Effects of caffeine and cyclopiazonic acid on contractile proteins of adult and newborn ferret cardiac fibres.

    abstract::Ventricular trabeculae from adult and newborn ferret heart were chemically skinned by Triton X-100 which disrupts all cellular membranes. In newborn preparations, maximal Ca(2+)-activated tension was two times smaller than in adult fibres while Ca2+ sensitivity was higher. Caffeine (10 mM) and cyclopiazonic acid (100 ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1996.0119

    authors: Bonnet V,Léoty C

    更新日期:1996-06-01 00:00:00

  • Microtubules mobility affects the modulation of L-type I(Ca) by muscarinic and beta-adrenergic agonists in guinea-pig cardiac myocytes.

    abstract::To investigate the interaction of cytoskeleton with the receptor modulation of ionic currents, we studied the effect of muscarinic and beta-adrenergic stimulation in adult guinea-pig ventricular cardiac myocytes treated with paclitaxel and colchicine, two drugs that respectively stabilize or destabilize microtubules. ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(02)00312-7

    authors: Malan D,Gallo MP,Bedendi I,Biasin C,Levi RC,Alloatti G

    更新日期:2003-02-01 00:00:00

  • Direct intracellular nitric oxide detection in isolated adult cardiomyocytes: flow cytometric analysis using the fluorescent probe, diaminofluorescein.

    abstract:UNLABELLED:We assessed the possibility to detect intracellular nitric oxide (NO) with the NO-specific probe 4,5-diaminofluorescein-2/diacetate (DAF-2/DA), by flow cytometry, in fresh adult rat cardiomyocytes, and compared the findings with results obtained from quantitation of cellular nitrate/nitrite (NO(x)) levels. ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2004.05.018

    authors: Strijdom H,Muller C,Lochner A

    更新日期:2004-10-01 00:00:00

  • Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy.

    abstract::The sulfur-containing beta-amino acid, taurine, is the most abundant free amino acid in cardiac and skeletal muscle. Although its physiological function has not been established, it is thought to play an important role in ion movement, calcium handling, osmoregulation and cytoprotection. To begin examining the physiol...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2008.03.001

    authors: Ito T,Kimura Y,Uozumi Y,Takai M,Muraoka S,Matsuda T,Ueki K,Yoshiyama M,Ikawa M,Okabe M,Schaffer SW,Fujio Y,Azuma J

    更新日期:2008-05-01 00:00:00

  • Potassium channel remodeling in cardiac hypertrophy.

    abstract::Cardiac hypertrophy is an adaptive process against increased work loads; however, hypertrophy also presents substrates for lethal ventricular arrhythmias, resulting in sudden arrhythmic deaths that account for about one third of deaths in cardiac hypertrophy. To maintain physiological cardiac function in the face of i...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2006.07.021

    authors: Furukawa T,Kurokawa J

    更新日期:2006-11-01 00:00:00

  • Autoantibodies from mothers of children with congenital heart block downregulate cardiac L-type Ca channels.

    abstract::Congenital heart block (CHB) affects offspring of mothers with autoantibodies (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that maternal anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize huma...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2001.1379

    authors: Qu Y,Xiao GQ,Chen L,Boutjdir M

    更新日期:2001-06-01 00:00:00

  • Quantitation and distribution of beta-tubulin in human cardiac myocytes.

    abstract::Increasing evidence suggests that derangements of cytoskeletal proteins contribute to alterations in intracellular signaling, myocyte function, and the coupling of myocytes to the extracellular matrix during cardiac hypertrophy and failure. Data from animal studies have shown an increased density of beta-tubulin prote...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.2002.2105

    authors: Aquila-Pastir LA,DiPaola NR,Matteo RG,Smedira NG,McCarthy PM,Moravec CS

    更新日期:2002-11-01 00:00:00

  • Inhibition of post-ischemic ventricular recovery by low concentrations of prostacyclin in isolated working rat hearts: dependency on concentration, ischemia duration, calcium and relationship to myocardial energy metabolism.

    abstract::The objective of this study was to characterize the effect of prostacyclin (PGI2) on ventricular function following total global ischemia in isolated working rat hearts and to investigate the mechanism of its action. Ischemia was initiated for 10, 15, 20 or 25 min with or without treatment with PGI2. Increasing durati...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(89)90749-9

    authors: Karmazyn M,Neely JR

    更新日期:1989-03-01 00:00:00

  • Ultrastructural changes induced in the isolated rat heart by enzymatically generated oxygen radicals.

    abstract::This study describes the effect of oxygen radicals on the ultrastructure of the isolated Langendorff-perfused rat heart. Oxygen radicals were enzymatically generated by xanthine oxidase (0.025 U/ml) and hypoxanthine (0.96 mM). Hearts were perfusion-fixed for electron microscopy and stereological technique was performe...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/s0022-2828(87)80583-7

    authors: Ytrehus K,Myklebust R,Olsen R,Mjøs OD

    更新日期:1987-04-01 00:00:00

  • 7-Ketocholesterol predisposes human aorta smooth muscle cells to Fas-mediated death.

    abstract::Human vascular smooth muscle cells (HVSMCs) are resistant to Fas-mediated death under normal physiological conditions. However, HVSMC death by activation of the receptor pathway was reported in the atherosclerotic lesions. In this study, we investigated whether 7-ketocholesterol, one of the major cholesterol oxides in...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2005.07.018

    authors: Rho MC,Kim YK,Chang JS,Lee HS,Baek JA,Chung MY,Lee HC,Lee HW,Rhim BY,Reidy MA,Kim K

    更新日期:2005-11-01 00:00:00

  • Antiplatelet monoclonal F(ab')2 antibody directed against the platelet GPIIb/IIIa receptor complex prevents coronary artery thrombosis in the canine heart.

    abstract::Interactions between platelets with injured vascular endothelium contribute to thrombotic occlusion. A murine monoclonal antibody [7E3 F(ab')2] to the platelet GPIIb/IIIa receptor complex was used to inhibit platelet aggregation in an experimental model of coronary artery thrombosis. Prevention of thrombotic occlusion...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(89)90650-0

    authors: Mickelson JK,Simpson PJ,Lucchesi BR

    更新日期:1989-04-01 00:00:00

  • Phospholipid reorganization and bilayer destabilization during myocardial ischemia and reperfusion: a hypothesis.

    abstract::The ultrastructure of myocardial tissue was studied during ischemia and reperfusion and during reperfusion with a calcium-containing solution after a short period of calcium-free perfusion (calcium paradox). After ischemia an aggregation of the sarcolemmal intramembranous particles was observed. Subsequent reperfusion...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(88)90335-5

    authors: Post JA,Ruigrok TJ,Verkleij AJ

    更新日期:1988-03-01 00:00:00

  • The late Na current as a therapeutic target: where are we?

    abstract::In this article we review the late Na current which functionally can be measured using patch-clamp electrophysiology (INa,late). This current is largely enhanced under pathological myocardial conditions such as ischemia and heart failure. In addition, INa,late can cause systolic and diastolic contractile dysfunction v...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2013.03.001

    authors: Maier LS,Sossalla S

    更新日期:2013-08-01 00:00:00

  • Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling.

    abstract::Forces associated with blood flow are crucial not only for blood vessel development but also for regulation of vascular pathology. Although there have been many studies characterizing the responses to mechanical stimuli, molecular mechanisms linking biological responses to mechanical forces remain unclear. Hic-5 (hydr...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2010.09.024

    authors: Kim-Kaneyama JR,Takeda N,Sasai A,Miyazaki A,Sata M,Hirabayashi T,Shibanuma M,Yamada G,Nose K

    更新日期:2011-01-01 00:00:00

  • Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine.

    abstract::There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxyge...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1998.0850

    authors: Lee JW,Miyawaki H,Bobst EV,Hester JD,Ashraf M,Bobst AM

    更新日期:1999-01-01 00:00:00

  • Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.

    abstract::Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic respo...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2012.10.014

    authors: Wong A,Grubb DR,Cooley N,Luo J,Woodcock EA

    更新日期:2013-01-01 00:00:00

  • Post-extrasystolic potentiation and the force-frequency relationship: differential augmentation of myocardial contractility in working myocardium from patients with end-stage heart failure.

    abstract::We studied post-extrasystolic potentiation (PESP) and frequency potentiation (FP) of human working myocardium isolated from the ventricles of 10 patients with end-stage heart failure (CHF) and 17 non-failing controls (CTL). The contractility index was peak isometric tension developed in vitro by trabeculae carneae (CT...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/0022-2828(90)90975-8

    authors: Phillips PJ,Gwathmey JK,Feldman MD,Schoen FJ,Grossman W,Morgan JP

    更新日期:1990-01-01 00:00:00

  • An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.

    abstract::In cardiomyocytes, Ca(2+) plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca(2+) within subcellular microdomains: transcription is regulated by Ca(2+) re...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.yjmcc.2014.06.015

    authors: Ibarra C,Vicencio JM,Varas-Godoy M,Jaimovich E,Rothermel BA,Uhlén P,Hill JA,Lavandero S

    更新日期:2014-10-01 00:00:00

  • Early remodeling of repolarizing K+ currents in the αMHC403/+ mouse model of familial hypertrophic cardiomyopathy.

    abstract::Familial hypertrophic cardiomyopathy (HCM), linked to mutations in myosin, myosin-binding proteins and other sarcolemmal proteins, is associated with increased risk of life threatening ventricular arrhythmias, and a number of animal models have been developed to facilitate analysis of disease progression and mechanism...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2017.01.006

    authors: Hueneke R,Adenwala A,Mellor RL,Seidman JG,Seidman CE,Nerbonne JM

    更新日期:2017-02-01 00:00:00

  • Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model.

    abstract:AIMS:Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to β-adrenergic receptor (β-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functio...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2019.05.025

    authors: Mika D,Bobin P,Lindner M,Boet A,Hodzic A,Lefebvre F,Lechène P,Sadoune M,Samuel JL,Algalarrondo V,Rucker-Martin C,Lambert V,Fischmeister R,Vandecasteele G,Leroy J

    更新日期:2019-08-01 00:00:00

  • Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats.

    abstract::To investigate the contribution of the cardiac renin-angiotensin system to ventricular dilatation after myocardial infarction, we examined the effects of 3-week treatments with an angiotensin converting enzyme inhibitor, delapril, and a selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on haemodynami...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1006/jmcc.1993.1149

    authors: Yamagishi H,Kim S,Nishikimi T,Takeuchi K,Takeda T

    更新日期:1993-11-01 00:00:00

  • A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia.

    abstract::Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition with a heterogeneous cardiac phenotype caused primarily by an expanded GAA trinucleotide repeat in the frataxin gene (FXN). FXN is important in mitochondrial iron efflux, sensitivity to oxidative stress, and cell death. The number of GAA re...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章

    doi:10.1016/j.yjmcc.2011.07.001

    authors: Kelly M,Bagnall RD,Peverill RE,Donelan L,Corben L,Delatycki MB,Semsarian C

    更新日期:2011-11-01 00:00:00