SOX6-SOCS3 regulates hypoxia-induced proliferation of HPASMCs by targeting STAT3 signaling pathway

Yu WANG; Shouxian WANG; Dewei CHEN; Bao LIU; Yuqi GAO

doi:10.16016/j.1000-5404.202009149

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SOX6-SOCS3 regulates hypoxia-induced proliferation of HPASMCs by targeting STAT3 signaling pathway

Basic Medicine | 更新时间：2026-01-09

- SOX6-SOCS3 regulates hypoxia-induced proliferation of HPASMCs by targeting STAT3 signaling pathway
- Journal of Third Military Medical University Vol. 43, Issue 4, Pages: 295-302(2021)
- 作者机构：
  
  1.400038 重庆，陆军军医大学（第三军医大学）高原军事医学系：高原特需药品与器材研究室
  2.400038 重庆，陆军军医大学（第三军医大学）高原军事医学系：病理生理学教研室
  3.400038 重庆，陆军军医大学（第三军医大学）高原军事医学系：极端环境医学教育部重点实验室
  4.400038 重庆，陆军军医大学（第三军医大学）高原军事医学系：全军高原医学重点实验室
- 作者简介：
- 基金信息：
  
  the Project of Logistic Science and Technology of PLA(AWS16J023)
- DOI：10.16016/j.1000-5404.202009149
  CLC： R322.121;R363.21;R364.31
- Received：19 September 2020，
  
  Revised：2020-10-16，
  
  Published：15 April 2021
- 稿件说明：
移动端阅览
Yu WANG, Shouxian WANG, Dewei CHEN, et al. SOX6-SOCS3 regulates hypoxia-induced proliferation of HPASMCs by targeting STAT3 signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(4): 295-302.
DOI：

Yu WANG, Shouxian WANG, Dewei CHEN, et al. SOX6-SOCS3 regulates hypoxia-induced proliferation of HPASMCs by targeting STAT3 signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(4): 295-302. DOI： 10.16016/j.1000-5404.202009149.

摘要

目的

探究SRY盒转录因子6（SRY-Box transcription factor 6，SOX6）-细胞因子信号转导抑制因子3（suppressor of cytokine signaling 3，SOCS3）在缺氧诱导的人肺动脉平滑肌细胞（human pulmonary artery smooth cells，HPASMCs）增殖中的作用及其可能机制。

方法

① 4%O

缺氧处理HPASMCs分为3组：常氧组、缺氧24 h组、缺氧48 h组（

=3）。②使用小RNA干扰SOX6或SOCS3表达，干扰SOX6表达分为4组：si-SOX6-NC组、si-SOX6-1组、si-SOX6-2组、si-SOX6-3组（

=3），干扰SOCS3表达分为3组：si-SOCS3-NC组、si-SOCS3-1组、si-SOCS3-2组（

=3）。③构建慢病毒过表达SOX6细胞后缺氧处理48 h，分为4组：常氧对照组、过表达SOX6组、缺氧对照组、缺氧+过表达SOX6组（n=3）。④采用CCK-8检测各组细胞增殖，RT-qPCR、Western blot检测各组SOX6、SOCS3、磷酸化信号转导与转录激活因子3（phosphorylated-signal transduction and activators of transcription 3，p-STAT3）、增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）的表达。

结果

缺氧可降低SOX6和SOCS3的表达（

0.01），不仅能诱导HPASMCs增殖（

0.05），还能显著上调p-STAT3、PCNA的表达（

0.05）。在常氧条件下，干扰SOX6或SOCS3可显著增强HPASMCs的增殖（

0.05），细胞中p-STAT3、PCNA的表达也显著升高（

0.01）。在缺氧条件下过表达SOX6可显著抑制缺氧诱导的HPASMCs增殖（

0.01），并显著降低p-STAT3、PCNA的表达（

0.01）。

结论

SOX6-SOCS3可抑制缺氧诱导的人肺动脉平滑肌细胞的增殖，其机制可能与抑制STAT3信号通路有关。

Abstract

Objective

To investigate the role of SRY-Box transcription factor 6 (SOX6)-suppressor of cytokine signaling 3 (SOCS3) on hypoxia-induced proliferation of human pulmonary artery smooth muscle cells (HPASMCs) and explore the possible mechanism.

Methods

① The HPASMCs were treated with 4% O

for 24 h or 48 h. ② siRNA was used to decrease the expression of SOX6 (si-SOX6-NC

si-SOX6-1

si-SOX6-2

si-SOX6-3) and SOCS3 (si-SOCS3-NC

si-SOCS3-1

si-SOCS3-2) in the cells. ③The HPASMCs with stable SOX6 overexpression induced by transfection with a lentiviral vector were exposed to hypoxia for 48 h

with the cells cultured in normoxia condition

or simple hypoxia condition as control. ④CCK-8 assay was used to testify the proliferation of the above groups of cells. The expression of SOX6

SOCS3

proliferating cell nuclear antigen (PCNA) and phosphorylated-signal transduction and activators of transcription 3 (p-STAT3) at mRNA and protein levels were detected by RT-qPCR and Western blotting

respectively.

Results

Hypoxia decreased the expression levels of SOX6 and SOCS3 (

0.01)

induced the proliferation of HPASMCs and up-regulated the levels of p-STAT3 and PCNA (

0.05). Under normoxia condition

the reduction of SOX6 or SOCS3 not only significantly increased the proliferation of HPASMCs (

0.05) butalso the levels of p-STAT3 and PCNA (

0.01). Under hypoxia

overexpression of SOX6 obviously suppressed hypoxia-induced proliferation and the expression levels of p-STAT3 and PCNA (

0.01).

Conclusion

SOX6-SOCS3 can suppress the hypoxia-induced proliferation of HPASMCs. Its mechanisms may be related to the inhibition of STAT3 signaling pathway.

关键词

Keywords

references

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