Gene Symbol: Ctf1
Description: cardiotrophin 1
Alias: CT-1, cardiotrophin-1
Species: mouse
Products:     Ctf1

Top Publications

  1. Latchman D. Cardiotrophin-1 (CT-1): a novel hypertrophic and cardioprotective agent. Int J Exp Pathol. 1999;80:189-96 pubmed
    ..CT-1 may therefore be of use as a novel cardio-protective agent, particularly if its hypertrophic effect can be specifically inhibited. ..
  2. Barnabe Heider F, Wasylnka J, Fernandes K, Porsche C, Sendtner M, Kaplan D, et al. Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1. Neuron. 2005;48:253-65 pubmed
  3. Oppenheim R, Wiese S, Prevette D, Armanini M, Wang S, Houenou L, et al. Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons. J Neurosci. 2001;21:1283-91 pubmed
    ..CT-1 is the first bona fide muscle-derived neurotrophic factor to be identified that is required for the survival of subgroups of developing motoneurons. ..
  4. Ishikawa M, Saito Y, Miyamoto Y, Kuwahara K, Ogawa E, Nakagawa O, et al. cDNA cloning of rat cardiotrophin-1 (CT-1): augmented expression of CT-1 gene in ventricle of genetically hypertensive rats. Biochem Biophys Res Commun. 1996;219:377-81 pubmed
  5. Lopez Andres N, Calvier L, Labat C, Fay R, Diez J, Benetos A, et al. Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice. Hypertension. 2013;61:120-9 pubmed publisher
    b>Cardiotrophin 1 (CT-1), an interleukin 6 family member, promotes fibrosis and arterial stiffness. We hypothesized that the absence of CT-1 influences arterial fibrosis and stiffness, senescence, and life span...
  6. Pennica D, Arce V, Swanson T, Vejsada R, Pollock R, Armanini M, et al. Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term survival of spinal motoneurons. Neuron. 1996;17:63-74 pubmed
    ..CT-1 may be important in normal motoneuron development and as a potential tool for slowing motoneuron degeneration in human diseases. ..
  7. Jiménez González M, Jaques F, Rodriguez S, Porciuncula A, Príncipe R, Abizanda G, et al. Cardiotrophin 1 protects beta cells from apoptosis and prevents streptozotocin-induced diabetes in a mouse model. Diabetologia. 2013;56:838-46 pubmed publisher
    b>Cardiotrophin 1 (CT-1) is a recently described cytokine originally isolated from the heart where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy...
  8. Funamoto M, Hishinuma S, Fujio Y, Matsuda Y, Kunisada K, Oh H, et al. Isolation and characterization of the murine cardiotrophin-1 gene: expression and norepinephrine-induced transcriptional activation. J Mol Cell Cardiol. 2000;32:1275-84 pubmed
    ..These data suggest that the CT-1 gene expression is regulated, at least partially, by transcriptional machinery. ..
  9. Ateghang B, Wartenberg M, Gassmann M, Sauer H. Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1alpha and intracellular reactive oxygen species. J Cell Sci. 2006;119:1043-52 pubmed
    ..Our results demonstrate that CT-1 expression in ES cells is regulated by ROS and HIF-1alpha and imply a crucial role of CT-1 in the survival and proliferation of ES-cell-derived cardiac cells. ..

More Information


  1. Miyake T, Alli N, Aziz A, Knudson J, Fernando P, Megeney L, et al. Cardiotrophin-1 maintains the undifferentiated state in skeletal myoblasts. J Biol Chem. 2009;284:19679-93 pubmed publisher
    ..The expression pattern of CT-1 in embryonic and post-natal skeletal muscle and in vivo effects of CT-1 on myogenesis implicate CT-1 in the maintenance of the undifferentiated state in muscle progenitor cells. ..
  2. Lopez Andres N, Iñigo C, Gallego I, Diez J, Fortuño M. Aldosterone induces cardiotrophin-1 expression in HL-1 adult cardiomyocytes. Endocrinology. 2008;149:4970-8 pubmed publisher
    ..In summary, ALDO induces CT-1 expression in adult HL-1 cardiomyocytes via genomic and nongenomic mechanisms. CT-1 up-regulation could have relevance in the direct hypertrophic effects of ALDO in cardiomyocytes. ..
  3. Marqués J, Belza I, Holtmann B, Pennica D, Prieto J, Bustos M. Cardiotrophin-1 is an essential factor in the natural defense of the liver against apoptosis. Hepatology. 2007;45:639-48 pubmed
    ..Our data show that CT-1 is a natural defense of the liver against apoptosis. This cytokine may have therapeutic potential. ..
  4. Gritman K, Van Winkle D, Lorentz C, Pennica D, Habecker B. The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response. Cytokine. 2006;36:9-16 pubmed
  5. Mascheck L, Sharifpanah F, Tsang S, Wartenberg M, Sauer H. Stimulation of cardiomyogenesis from mouse embryonic stem cells by nuclear translocation of cardiotrophin-1. Int J Cardiol. 2015;193:23-33 pubmed publisher
    ..Nuclear translocation of CT-1 regulates cardiomyogenesis of ES cells and involves calcium, NO, ROS as well as CT-1 regulated signaling pathways. ..
  6. Lopez Andres N, Martin Fernandez B, Rossignol P, Zannad F, Lahera V, Fortuño M, et al. A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone. Am J Physiol Heart Circ Physiol. 2011;301:H2372-82 pubmed publisher
    ..CT-1-null mice were resistant to Aldo-induced LVH and fibrosis. These data suggest a key role for CT-1 in cardiac remodeling induced by Aldo independent of changes in blood pressure levels. ..
  7. Walker E, McGregor N, Poulton I, Pompolo S, Allan E, Quinn J, et al. Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling. J Bone Miner Res. 2008;23:2025-32 pubmed publisher
    ..CT-1 may now be classed as an essential osteoclast-derived stimulus of both bone formation and resorption. ..
  8. Gard A, Gavin E, Solodushko V, Pennica D. Cardiotrophin-1 in choroid plexus and the cerebrospinal fluid circulatory system. Neuroscience. 2004;127:43-52 pubmed
    ..A rationale for studies examining CT-1-deficient mice in these respects is provided by the data. ..
  9. Pennica D, King K, Shaw K, Luis E, Rullamas J, Luoh S, et al. Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci U S A. 1995;92:1142-6 pubmed
    ..5-kDa protein, cardiotrophin 1, that potently induces cardiac myocyte hypertrophy in vitro...
  10. Arce V, Pollock R, Philippe J, Pennica D, Henderson C, Delapeyriere O. Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J Neurosci. 1998;18:1440-8 pubmed
    ..The possibility that they act together on individual motoneurons suggests that the motoneuron must integrate distinct signals from different cellular partners when deciding whether to die or to survive. ..
  11. Richards C, Kerr C, Tanaka M, Hara T, Miyajima A, Pennica D, et al. Regulation of tissue inhibitor of metalloproteinase-1 in fibroblasts and acute phase proteins in hepatocytes in vitro by mouse oncostatin M, cardiotrophin-1, and IL-6. J Immunol. 1997;159:2431-7 pubmed
    ..These results also suggest that mOSM is an important cytokine in inflammation, through modulation of fibroblast function as well as hepatocyte responses. ..
  12. Pennica D, Swanson T, Shaw K, Kuang W, Gray C, Beatty B, et al. Human cardiotrophin-1: protein and gene structure, biological and binding activities, and chromosomal localization. Cytokine. 1996;8:183-9 pubmed
    ..7 kb CT-1 mRNA is expressed in adult human heart, skeletal muscle, ovary, colon, prostate and testis and in fetal kidney and lung. The coding region of CT-1 is contained on three exons and is located on human chromosome 16p11.1-16p11.2. ..
  13. Sheng Z, Pennica D, Wood W, Chien K. Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Development. 1996;122:419-28 pubmed
    ..Thus, CT-1 may play an autocrine role during cardiac chamber growth and morphogenesis by promoting the survival and proliferation of immature myocytes, most likely via gp130-dependent signaling pathways. ..
  14. López Yoldi M, Marcos Gómez B, Romero Lozano M, Sainz N, Prieto J, Martinez J, et al. Cardiotrophin-1 Regulates Adipokine Production in 3T3-L1 Adipocytes and Adipose Tissue From Obese Mice. J Cell Physiol. 2017;232:2469-2477 pubmed publisher
    ..J. Cell. Physiol. 232: 2469-2477, 2017. © 2016 Wiley Periodicals, Inc. ..
  15. López Yoldi M, Stanhope K, Garaulet M, Chen X, Marcos Gómez B, Carrasco Benso M, et al. Role of cardiotrophin-1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24-h circulating CT-1 profiles in normal-weight and overweight/obese subjects. FASEB J. 2017;31:1639-1649 pubmed publisher
    ..Moreno-Aliaga, M. J. Role of cardiotrophin-1 in the regulation of metabolic circadian rhythms and adipose core clock genes in mice and characterization of 24-h circulating CT-1 profiles in normal-weight and overweight/obese subjects. ..
  16. Castaño D, Larequi E, Belza I, Astudillo A, Martinez Ansó E, Balsinde J, et al. Cardiotrophin-1 eliminates hepatic steatosis in obese mice by mechanisms involving AMPK activation. J Hepatol. 2014;60:1017-25 pubmed publisher
    ..In vitro studies showed that these effects are mediated by activated AMPK. rCT-1 resolves hepatic steatosis in obese mice by mechanisms involving AMPK activation. rCT-1 deserves consideration as a potential therapy for NAFLD. ..
  17. Wang D, Liu X, Liu Y, Li S, Wang C. The Effects of Cardiotrophin-1 on Early Synaptic Mitochondrial Dysfunction and Synaptic Pathology in APPswe/PS1dE9 Mice. J Alzheimers Dis. 2017;59:1255-1267 pubmed publisher
    ..These results suggest that CT-1 may be a potent candidate for the early prevention and treatment of AD. ..
  18. Wang D, Li X, Gao K, Lu D, Zhang X, Ma C, et al. Cardiotrophin-1 (CTF1) ameliorates glucose-uptake defects and improves memory and learning deficits in a transgenic mouse model of Alzheimer's disease. Pharmacol Biochem Behav. 2013;107:48-57 pubmed publisher
    Cardiotrophin-1 (CTF1) has been reported to act as a trophic factor for a few neurons, such as sensory, cholinergic, dopaminergic, motor and cortical neurons...
  19. Bortolotti F, Ruozi G, Falcione A, Doimo S, Dal Ferro M, Lesizza P, et al. In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment Factor for Mesenchymal Stromal Cells. Circulation. 2017;136:1509-1524 pubmed publisher
  20. Moreno Aliaga M, Pérez Echarri N, Marcos Gómez B, Larequi E, Gil Bea F, Viollet B, et al. Cardiotrophin-1 is a key regulator of glucose and lipid metabolism. Cell Metab. 2011;14:242-53 pubmed publisher
    ..We conclude that CT-1 is a master regulator of fat and glucose metabolism with potential applications for treatment of obesity and insulin resistance. ..
  21. Robador P, San José G, Rodriguez C, Guadall A, Moreno M, Beaumont J, et al. HIF-1-mediated up-regulation of cardiotrophin-1 is involved in the survival response of cardiomyocytes to hypoxia. Cardiovasc Res. 2011;92:247-55 pubmed publisher
    ..However, no evidence for a direct regulation of CT-1 gene (CTF1) promoter by hypoxia inducible factor-1 (HIF-1) has been provided...
  22. Iñiguez M, Berasain C, Martinez Ansó E, Bustos M, Fortes P, Pennica D, et al. Cardiotrophin-1 defends the liver against ischemia-reperfusion injury and mediates the protective effect of ischemic preconditioning. J Exp Med. 2006;203:2809-15 pubmed
    ..In conclusion, CT-1 is an essential endogenous defense of the liver against I/R and is a key mediator of the protective effect induced by IP. ..
  23. Holtmann B, Wiese S, Samsam M, Grohmann K, Pennica D, Martini R, et al. Triple knock-out of CNTF, LIF, and CT-1 defines cooperative and distinct roles of these neurotrophic factors for motoneuron maintenance and function. J Neurosci. 2005;25:1778-87 pubmed
  24. Sauer H, Neukirchen W, Rahimi G, Grünheck F, Hescheler J, Wartenberg M. Involvement of reactive oxygen species in cardiotrophin-1-induced proliferation of cardiomyocytes differentiated from murine embryonic stem cells. Exp Cell Res. 2004;294:313-24 pubmed
    ..It is concluded that CT-1 stimulates the proliferation of ES cell-derived cardiomyocytes by signaling pathways that involve ROS as signaling molecules in the signal transduction cascade. ..
  25. Natal C, Fortuño M, Restituto P, Bazán A, Colina I, Diez J, et al. Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome. Am J Physiol Endocrinol Metab. 2008;294:E52-60 pubmed
    ..2, P < 0.05). Taken together, our data suggest that adipose tissue can be recognized as a source of CT-1, which could account for the high circulating levels of CT-1 in patients with MS. ..
  26. López Yoldi M, Fernández Galilea M, Laiglesia L, Larequi E, Prieto J, Martínez J, et al. Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases. J Lipid Res. 2014;55:2634-43 pubmed publisher
    ..These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects. ..
  27. Oberle S, Schober A, Meyer V, Holtmann B, Henderson C, Sendtner M, et al. Loss of leukemia inhibitory factor receptor beta or cardiotrophin-1 causes similar deficits in preganglionic sympathetic neurons and adrenal medulla. J Neurosci. 2006;26:1823-32 pubmed
    ..Thus, both somatic motoneurons and PSNs in the spinal cord depend on LIFRbeta signaling for their development and maintenance, although PSNs seem to be overall less affected than somatic motoneurons by LIFRbeta deprivation...
  28. Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, et al. ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci U S A. 2005;102:9182-7 pubmed
    ..Our data strongly suggest that this protease constitutes a major regulatory element for the multiple functions of E-cadherin under physiological as well as pathological conditions. ..
  29. Derouet D, Rousseau F, Alfonsi F, Froger J, Hermann J, Barbier F, et al. Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor. Proc Natl Acad Sci U S A. 2004;101:4827-32 pubmed publisher
    ..Thus, NP is a new ligand for CNTFRalpha, with important implications for murine nervous system development...