Abstract
The binding of ligands to gp130 activates the JAK/STAT signal transduction pathway, in which STAT3 plays a central role in transmitting signals from the cell membrane to the nucleus. Since cardiac-specific disruption of gp130 has been shown to present heart failure in response to mechanical stress, inactivation of STAT3 resulting from the loss of gp130 may be a key event in the transition from cardiac hypertrophy to heart failure.
Proper vascular growth is essential for normal cardiac development and the remodeling process. VEGF, which is reported to play an important role in the maintenance of cardiac function by restoration of oxygen deprivation during the remodeling process, has been identified as a target gene of STAT3. In this review, STAT3 is highlighted as a regulator of angiogenic factors and the novel role of the STAT3-mediated signaling pathway in regulation of vasculogenesis is demonstrated. Activation of gp130/STAT pathway is proposed as a novel therapeutic strategy for prevention of cardiac remodeling.
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References
Kishimoto T, Akira S, Narazaki M, Taga T. 1995. Interleukin-6 family of cytokines and gp130. Blood 86:1243–1254.
Kunisada K, Hirota H, Fujio Y, Matsui H, Tani Y, Yamauchi-Takihara K, Kishimoto T. 1996. Activation of JAK-STAT and MAP kinases by leukemia inhibitory factor through gp130 in cardiac myocytes. Circulation 94:2626–2632.
Oh H, Fujio Y, Kunisada K, Hirota H, Matsui H, Kishimoto T, Yamauchi-Takihara K. 1998. Activation of phosphatidylinositol 3-kinase through glycoprotein 130 induces protein kinase B and p70 S6 kinase phosphorylation in cardiac myocytes. J Biol Chem 273:9703–9710.
Pan J, Fukuda K, Saito M, Matsuzaki J, Kodama H, Sano M, Takahashi T, Kato T, Ogawa S. 1999. Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes. Circ Res 84:1127–1136.
Hishinuma S, Funamoto M, Fujio Y, Kunisada K, Yamauchi-Takihara K. 1999. Hypoxic stress induces cardiotrophin-1 expression in cardiac myocytes. Biochem Biophys Res Commun 264:436–440.
Yamauchi-Takihara K, Kishimoto T. 2000. Cytokine and their receptors in cardiovascular diseases-role of gp130 signalling pathway in cardiac myocyte growth and maintenance. Int J Exp Path 81:1–16.
Hirota H, Chen J, Betz UA, Rajewski K, Gu Y, Ross J Jr., Muller W, Chien KR. 1999. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97:189–198.
Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MWN. 1996. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442.
Carmeliet P, Ng YS, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I, Ehler E, Kakkar W, Stalmans I, Mattot V, Perriard JC, Dewerchin M, Flameng W, Nagy A, Lupu F, Moons L, Collen D, D’Amore PA, Shima DT. 1999. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF 164 and VEGF 188. Nat Med 5:495–502.
Giordano FJ, Gerber H-P, Williams S-P, VanBruggen N, Bunting S, Ruiz-Lozano P, Gu Y, Nath AK, Huang Y, Hickey R, Dalton N, Peterson KL, Ross J Jr, Chien KR, Ferrara N. 2001. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA 98:5780–5785.
Coral-Vazquez R, Cohn RD, Moore SA, Hill JA, Weiss RM, Davisson RL, Straub V, Barresi R, Bansal D, Hrstka RF, Williamson R, Campbell KP. 1999. Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: A novel mechanism for cardiomyopathy and muscular dystrophy. Cell 98:465–474.
Funamoto M, Fujio Y, Kunisada K, Negoro S, Tone E, Osugi T, Hirota H, Izumi M, Yoshizaki K, Walsh K, Kishimoto T, Yamauchi-Takihara K. 2000. Signal transducer and activator of transcription 3 is required for glycoprotein 130-mediated induction of vascular endothelial growth factor in cardiac myocytes. J Biol Chem 275:10561–10566.
Osugi T, Oshima Y, Fujio Y, Funamoto M, Yamashita A, Negoro S, Kunisada K, Izumi M, Nakaoka Y, Hirota H, Okabe M, Yamauchi-Takihara K, Kawase I, Kishimoto T. 2002. Cardiac-specific activation of signal transducer and activator of transcription 3 promotes vascular formation in the heart. J Biol Chem 277:6676–6681.
Yamauchi-Takihara K, Ihara Y, Ogata A, Yoshizaki K, Azuma J, Kishimoto T. 1995. Hypoxic stress induced cardiac myocyte derived interleukin-6. Circulation 91:1520–1524.
Funamoto M, Hishinuma S, Fujio Y, Matsuda Y, Kunisada K, Oh H, Negoro S, Tone E, Kishimoto T, Yamauchi-Takihara K. 2000. Isolation and characterization of the murine cardiotrophin-1 gene: expression and norepinephrine-induced transcriptional activation. J Mol Cell Cardiol 32:1275–1284.
Pan J, Fukuda K, Kodama H, Sano M, Takahashi T, Makino S, Kato T, Manabe T, Hori S, Ogawa S. 1998. Involvement of gp 130-mediated signaling in pressure overload-induced activation of the JAK/STAT pathway in rodent heart. Heart Vessels 13:199–208.
Aoyama T, Takimoto Y, Pennica D, Inoue R, Shinoda E, Hattori R, Yui Y, Sasayama S. 2000. Augmented expression of cardiotrophin-1 and its receptor component, gp130, in both left and right ventricles after myocardial infarction in the rat. J Mol Cell Cardiol 32:1821–1830.
Jougasaki M, Tachibana I, Luchner A, Leskinen H, Redfield MM, Burnett JC. 2000. Augmented cardiac cardiotrophin-1 in experimental congestive heart failure. Circulation 101:14–17.
Fujio Y, Kunisada K, Hirota H, Yamauchi-Takihara K, Kishimoto T. 1997. Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes. J Clin Invest 99:2898–2905.
Negoro S, Kunisada K, Fujio Y, Funamoto M, Darville MI, Eizirik DL, Osugi T, Izumi M, Oshima Y, Nakaoka Y, Hirota H, Kishimoto T, Yamauchi-Takihara K. 2001. Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase. Circulation 104:979–981.
Xuan YT, Guo Y, Han H, Zhu Y, Bolli R. 2001. An essential role of the JAK-STAT pathway in ischemic preconditioning. Proc Natl Acad Sci USA 98:9050–9055.
Yamauchi-Takihara K, Kishimoto T. 2000. A novel role for STAT 3 in cardiac remodeling. Trends Cardiovasc Med 10:298–303.
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Yamauchi-Takihara, K., Hirota, H., Fujio, Y., Izumi, M., Oshima, Y., Nakaoka, Y. (2003). A Novel Role for Cytokine Signaling in Cardiac Remodeling. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_17
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DOI: https://doi.org/10.1007/978-1-4419-9262-8_17
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