Activation of gp130 transduces hypertrophic signals via STAT3 in cardiac myocytes

Article; Proceedings Paper

关键词: LEUKEMIA INHIBITORY FACTOR;    ATRIAL NATRIURETIC FACTOR;    MUSCLE CELL HYPERTROPHY;    PROTEIN-KINASE;    GENE-EXPRESSION;    PRESSURE-OVERLOAD;    VENTRICULAR HYPERTROPHY;    RECOMBINANT ADENOVIRUS;    HEART-CELLS;    GROWTH;   

DOI  :  10.1161/01.CIR.98.4.346

来源: SCIE

【 摘 要 】

Background-gp130, a signal transducer of the IL-6-related cytokines, is expressed ubiquitously, including in the heart. The activation of gp130 in cardiac myocytes was reported to induce myocardial hypertrophy. The downstream side of gp130 consists of two distinct pathways in cardiac myocytes, one a Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, the other a mitogen-activated protein kinase (MAPK) pathway. In the present study, we examined whether the JAK/STAT pathway, especially the STAT3-mediated pathway, plays a critical role in gp130-dependent myocardial hypertrophy by transfecting wild-type and mutated-type STAT3 cDNA to cardiac myocytes. Methods and Results-We constructed three I;inds of replication-defective adenovirus vectors carrying wild-type (AD/WT) or mutated-type (AD/DN) STAT3 cDNA or adenovirus vector itself (AD). Cultured murine cardiac myocytes infected with adenovirus were stimulated with leukemia inhibitory factor (LIF), and the expression of c-Sos and atrial natriuretic factor (ANF) mRNAs and [H-3]leucine incorporation were examined. There were no significant differences in MAPK activity among the three groups. Compared with AD-transfected cardiac myocytes, induction of c-Sos and ANF mRNAs and protein synthesis after LIF stimulation were significantly augmented in AD/WT-transfected cells. In contrast, induction of c-Sos and ANF mRNA expression and protein synthesis were attenuated after LIF stimulation in cardiac myocytes transfected with AD/DN. Conclusions-These results suggest that the STAT3-dependent signaling pathway downstream of gp 130 promotes cardiac myocyte hypertrophy under stimulation with LIF.

【 授权许可】

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