title: Effects and mechanism of organ protection by cardiotrophin-1.
abstract: Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 family, is reported to exhibit a plethora of pleiotropic effects in the heart such as cytoprotective, pro-proliferative and pro-fibrotic ones. An extensive research has been devoted on proliferative and profibrotic effects of CT-1 on the heart. Thus the present review has been aimed to critically define the cytoprotective effects of CT-1 and the cellular and molecular mechanisms involved in them. Although many effects of CT-1 have been described on the heart, CT-1 has now also been reported to exhibit important protective effects in other organs such as liver, kidney or nervous system. CT-1 produces its effects through a unique receptor system comprising LIF receptor (LIFRβ) and a common signal transducer, the glycoprotein 130 (gp130). The signaling pathway downstream from gp130 is based on at least, three distinct pathways: 1) the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, 2) the p42/44 mitogen-activated protein kinase (p42/44 MAPK) pathway, also known as the extracellular receptor kinase-1/2 (ERK1/2) pathway, and 3) the phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. Since CT-1 easily achieves its cytoprotective effects via a combination of the above three signaling pathways, it becomes quite necessary to determine which pathway(s) is involved in each particular effect of CT-1. In each of its target organs, CT-1 may also display differential mechanisms of cytoprotection, and thus it is relevant to understand how these mechanisms are locally regulated.
authors.affiliation: Department of Surgery, University of Salamanca, Salamanca, Spain.
authors.forename: Ma B
authors.initials: MB
authors.lastname: García-Cenador
authors.forename: J M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.forename: J
authors.initials: J
authors.lastname: Díez
authors.forename: F J
authors.initials: FJ
authors.lastname: García-Criado
mesh_terms: D002316:Cardiotonic Agents / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; C092073:cardiotrophin 1