gp130 signaling pathways: Recent advances and implications for cardiovascular disease

gp130 was initially identified as a signal-transducing receptor component that associates with the interleukin 6 receptor (IL-6R) when the receptor is occupied by interleukin 6 (IL-6). It has been revealed that the receptor complexes for IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OM), and ciliary neurotrophic factor (CNTF) utilize this gp130 protein as a common signal-transducing component, explaining how these cytokines mediate overlapping biological function. Recent observations with mice lacking gp130 or having continuously activated gp130 protein have disclosed an important biological function of gp130 in cardiovascular system: the former mice show extremely hypoplastic development of the ventricular myocardium at 16.5 days postcoitum (dpc), and the latter exhibit hypertrophy of myocardium. These cardiovascular abnormalities are considered to be the results of the perturbation of gp130, which also transduces the signal of cardiotrophin-1 (CT-1), a recently isolated factor causing hypertrophy in cultured cardiomyocytes and having sequence similarity with IL-6, IL-11, LIF, CNTF, and OM. In fact, CT-1 shares gp130 with these cytokines as a critical signaling component. Besides various well-established mechanisms by which cardiac growth and development are regulated, a gp130 signaling may be a newly discovered mechanism that regulates these events.