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Updated: Aug 16, 2026
Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells
Li Bai1, Zubin Yu, Guisheng Qian
1Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China.
Abstract:
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 2h 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.
Insights
Hypoxia activates STAT3 signaling and smooth muscle cell proliferation. Suppressors of Cytokine Signaling 3 (SOCS3) is induced by hypoxia and inhibits this STAT3 pathway and cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Cytokine signaling regulates cell function, with JAK-STAT pathway playing a key role.
- Suppressors of Cytokine Signaling (SOCS) proteins are emerging as critical negative regulators of cytokine signaling.
- SOCS proteins are known to inhibit the JAK-STAT pathway through distinct mechanisms.
Purpose of the Study:
- To investigate the role of SOCS proteins in hypoxia-induced pulmonary vascular smooth muscle cell (PASMC) activation.
- To determine the effect of hypoxia on STAT3 phosphorylation and SOCS gene expression in PASMCs.
- To elucidate the functional impact of SOCS3 on hypoxia-induced PASMC proliferation.
Main Methods:
- Primary rat pulmonary vascular smooth muscle cells (PASMCs) were cultured and subjected to hypoxic conditions.
- STAT3 phosphorylation and c-myc gene transcription were measured.
- Messenger RNA (mRNA) levels for SOCS1 and SOCS3 were quantified.
- Forced expression of SOCS3 gene was performed to assess its inhibitory effects.
- PASMC proliferation was measured under normoxic and hypoxic conditions with and without SOCS3 overexpression.
Main Results:
- Hypoxia significantly increased STAT3 phosphorylation (up to four-fold) and PASMC proliferation (nearly two-fold).
- Hypoxia markedly induced SOCS3 mRNA expression within 2 hours, but not SOCS1.
- Forced SOCS3 expression suppressed hypoxia-induced STAT3 phosphorylation (>70%) and c-myc transcription (>60%).
- SOCS3 overexpression downregulated hypoxia-induced PASMC proliferation by approximately 50%.
Conclusions:
- The STAT3-dependent pathway is involved in hypoxia-stimulated PASMC activation and proliferation.
- SOCS3 is a rapidly hypoxia-inducible gene in PASMCs.
- SOCS3 acts as a negative feedback regulator, inhibiting the cellular signaling pathway activated by hypoxia.
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