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Gene Review

Ctf1  -  cardiotrophin 1

Mus musculus

Synonyms: CT-1, Cardiotrophin-1
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Disease relevance of Ctf1


Psychiatry related information on Ctf1


High impact information on Ctf1

  • Overall, 40-70% of IEL from either thymus-bearing or athymic mice expressed the cytotoxic activation antigen, CT-1, and the J11d lymphocyte marker, both of which were associated with a population of Thy-1-, Lyt-2+ cytotoxic IEL [7].
  • Hepatocytes cultured under serum starvation or stimulated with the pro-apoptotic cytokine transforming growth factor beta (TGF-beta) produce CT-1, which behaves as an autocrine/paracrine survival factor [3].
  • In this study, we investigated the expression of CT-1 by liver cells and its possible hepatoprotective properties [3].
  • RESULTS: We found that CT-1 is up-regulated during liver regeneration and exerts potent antiapoptotic effects on hepatocytic cells [3].
  • Furthermore, binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after CT-1 stimulation [8].

Chemical compound and disease context of Ctf1


Biological context of Ctf1


Anatomical context of Ctf1


Associations of Ctf1 with chemical compounds

  • The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice [2].
  • The effect of CT-1 seems to be direct as it also inhibited TNF production when added to whole mouse blood cultured with lipopolysaccharide [16].
  • Cardiotrophin-like cytokine labelling using Bir A biotin ligase: a sensitive tool to study receptor expression by immune and non-immune cells [17].
  • The expression of CT-1, a murine CTL activation antigen, and asialo GM1, a murine NK cell marker, were variable on IEL clones, and their presence did not correlate with the changes in lytic behavior [18].

Physical interactions of Ctf1

  • We did not find any difference between JVS and control mice at 2 weeks in the mRNA level of ventricular leukemia inhibitory factor (LIF) which binds to the same receptor as CT-1 [2].

Regulatory relationships of Ctf1

  • 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 [1].
  • CT-1-induced astrocyte differentiation was solely gp130-dependent [19].
  • In the present study, we demonstrate that treatment of embryoid bodies grown from pluripotent murine embryonic stem (ES) cells with CT-1 significantly stimulated cardiomyogenesis and increased nuclear expression of the proliferation marker Ki-67 [20].

Other interactions of Ctf1

  • Mouse OSM, LIF and CT-1 strongly induced the formation of tartrate resistant acid phosphatase positive (TRAP(+)) multinucleated cells (MNC) in a dose-dependent fashion [12].
  • In cntf/lif/ct-1 triple-knock-out mice, various degrees of muscle fiber type grouping are found, indicating that denervation and reinnervation had occurred [15].
  • We show that LIF, CNTF, and CT-1 are synthesized in embryonic adrenal gland and spinal cord and that PSNs express LIFRbeta [14].
  • 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 [13].
  • Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1alpha and intracellular reactive oxygen species [1].

Analytical, diagnostic and therapeutic context of Ctf1

  • DEX (10(-7) M) costimulation also synergistically enhanced TRAP(+)cell numbers of LIF, and CT-1 treated cocultures [12].
  • The CT-1 mRNA level was quantitatively measured by the competitive RT-PCR method [2].
  • We also investigated whether CT-1 might exert protective effects in animal models of liver damage [3].
  • Confocal laser microscopy of CT-1 stimulated cells reveals the assembly of sarcomeric units in series rather than in parallel, as seen after alpha-adrenergic stimulation [21].
  • Similarly, Western blotting showed a twofold elevation of CT-1 protein in infected animals (P < 0.025) [22].


  1. Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1alpha and intracellular reactive oxygen species. Ateghang, B., Wartenberg, M., Gassmann, M., Sauer, H. J. Cell. Sci. (2006) [Pubmed]
  2. The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice. Yoshida, G., Horiuchi, M., Kobayashi, K., Jalil, M.D., Iijima, M., Hagihara, S., Nagao, N., Saheki, T. In Vivo (2000) [Pubmed]
  3. Protection against liver damage by cardiotrophin-1: a hepatocyte survival factor up-regulated in the regenerating liver in rats. Bustos, M., Beraza, N., Lasarte, J.J., Baixeras, E., Alzuguren, P., Bordet, T., Prieto, J. Gastroenterology (2003) [Pubmed]
  4. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy. Kunisada, K., Negoro, S., Tone, E., Funamoto, M., Osugi, T., Yamada, S., Okabe, M., Kishimoto, T., Yamauchi-Takihara, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. A heart-specific increase in cardiotrophin-1 gene expression precedes the establishment of ventricular hypertrophy in genetically hypertensive rats. Ishikawa, M., Saito, Y., Miyamoto, Y., Harada, M., Kuwahara, K., Ogawa, E., Nakagawa, O., Hamanaka, I., Kajiyama, N., Takahashi, N., Masuda, I., Hashimoto, T., Sakai, O., Hosoya, T., Nakao, K. J. Hypertens. (1999) [Pubmed]
  6. A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity. Kraves, S., Weitz, C.J. Nat. Neurosci. (2006) [Pubmed]
  7. Ontogeny of the Thy-1-, Lyt-2+ murine intestinal intraepithelial lymphocyte. Characterization of a unique population of thymus-independent cytotoxic effector cells in the intestinal mucosa. Klein, J.R. J. Exp. Med. (1986) [Pubmed]
  8. Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein. Pradervand, S., Yasukawa, H., Muller, O.G., Kjekshus, H., Nakamura, T., St Amand, T.R., Yajima, T., Matsumura, K., Duplain, H., Iwatate, M., Woodard, S., Pedrazzini, T., Ross, J., Firsov, D., Rossier, B.C., Hoshijima, M., Chien, K.R. EMBO J. (2004) [Pubmed]
  9. Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin I2 receptor. Hara, A., Yuhki, K., Fujino, T., Yamada, T., Takayama, K., Kuriyama, S., Takahata, O., Karibe, H., Okada, Y., Xiao, C.Y., Ma, H., Narumiya, S., Ushikubi, F. Circulation (2005) [Pubmed]
  10. Cardiotrophin-1 requires LIFRbeta to promote survival of mouse motoneurons purified by a novel technique. Arce, V., Garces, A., de Bovis, B., Filippi, P., Henderson, C., Pettmann, B., deLapeyrière, O. J. Neurosci. Res. (1999) [Pubmed]
  11. The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response. Gritman, K., Van Winkle, D.M., Lorentz, C.U., Pennica, D., Habecker, B.A. Cytokine (2006) [Pubmed]
  12. Stimulation of osteoclast differentiation in vitro by mouse oncostatin M, leukaemia inhibitory factor, cardiotrophin-1 and interleukin 6: synergy with dexamethasone. Richards, C.D., Langdon, C., Deschamps, P., Pennica, D., Shaughnessy, S.G. Cytokine (2000) [Pubmed]
  13. Cardiotrophin-1, a muscle-derived cytokine, is required for the survival of subpopulations of developing motoneurons. Oppenheim, R.W., Wiese, S., Prevette, D., Armanini, M., Wang, S., Houenou, L.J., Holtmann, B., Gotz, R., Pennica, D., Sendtner, M. J. Neurosci. (2001) [Pubmed]
  14. Loss of leukemia inhibitory factor receptor beta or cardiotrophin-1 causes similar deficits in preganglionic sympathetic neurons and adrenal medulla. Oberle, S., Schober, A., Meyer, V., Holtmann, B., Henderson, C., Sendtner, M., Unsicker, K. J. Neurosci. (2006) [Pubmed]
  15. Triple knock-out of CNTF, LIF, and CT-1 defines cooperative and distinct roles of these neurotrophic factors for motoneuron maintenance and function. Holtmann, B., Wiese, S., Samsam, M., Grohmann, K., Pennica, D., Martini, R., Sendtner, M. J. Neurosci. (2005) [Pubmed]
  16. Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharide-treated mice and in vitro in mouse blood cells. Benigni, F., Sacco, S., Pennica, D., Ghezzi, P. Am. J. Pathol. (1996) [Pubmed]
  17. Cardiotrophin-like cytokine labelling using Bir A biotin ligase: a sensitive tool to study receptor expression by immune and non-immune cells. Cognet, I., Guilhot, F., Gabriac, M., Chevalier, S., Chouikh, Y., Herman-Bert, A., Guay-Giroux, A., Corneau, S., Magistrelli, G., Elson, G.C., Gascan, H., Gauchat, J.F. J. Immunol. Methods (2005) [Pubmed]
  18. Spontaneous in vitro evolution of lytic specificity of cytotoxic T lymphocyte clones isolated from murine intestinal epithelium. Klein, J.R., Kagnoff, M.F. J. Immunol. (1987) [Pubmed]
  19. Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin-1-induced activation of STAT3. Ochiai, W., Yanagisawa, M., Takizawa, T., Nakashima, K., Taga, T. Cytokine (2001) [Pubmed]
  20. Involvement of reactive oxygen species in cardiotrophin-1-induced proliferation of cardiomyocytes differentiated from murine embryonic stem cells. Sauer, H., Neukirchen, W., Rahimi, G., Grünheck, F., Hescheler, J., Wartenberg, M. Exp. Cell Res. (2004) [Pubmed]
  21. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. Wollert, K.C., Taga, T., Saito, M., Narazaki, M., Kishimoto, T., Glembotski, C.C., Vernallis, A.B., Heath, J.K., Pennica, D., Wood, W.I., Chien, K.R. J. Biol. Chem. (1996) [Pubmed]
  22. Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic cardiomyopathy. Chandrasekar, B., Melby, P.C., Pennica, D., Freeman, G.L. Immunol. Lett. (1998) [Pubmed]
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