کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2848669 | 1167435 | 2006 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells](/preview/png/2848669.png)
Recently identified suppressors of cytokine signaling (SOCS) have been proposed as negative regulators of cytokine signaling, which have distinct mechanisms of inhibiting JAK-STAT pathway. In this study, using cultures of rat primary pulmonary vascular smooth muscle cells (PASMC), we found that hypoxia induced strongly STAT3 phosphorylation by up to four-fold. At the same time, mRNA for the endogenous cytokine signaling repressor SOCS3, but not SOCS1, was markedly induced in PASMC as early as 2 h following hypoxic stimulation. Furthermore, forced expression of SOCS3 gene suppressed tyrosine phosphorylation of STAT3 and transcription of c-myc gene by more than 70% and 60% in PASMC under hypoxic conditions, respectively. Additionally, we showed here that hypoxia enhanced nearly two-fold increase of PASMC proliferation and overexpression of SOCS3 gene downregulated hypoxia-induced PASMC proliferation by about 50%. The finding suggest that STAT3-dependent pathway is involved in the activation and proliferation of PASMC stimulated by hypoxia, and SOCS3 is a rapidly hypoxia-inducible gene and acts to inhibit activation of cellular signaling pathway in a classical negative feedback loop.
Journal: Respiratory Physiology & Neurobiology - Volume 152, Issue 1, May 2006, Pages 83–91