SOX6-SOCS3通过STAT3信号通路调控缺氧诱导的人肺动脉平滑肌细胞增殖  

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

作　　者：王羽 王授衔 陈德伟[2,3,4] 刘宝[1,3,4] 高钰琪[1,3,4] WANG Yu;WANG Shouxian;CHEN Dewei;LIU Bao;GAO Yuqi(Department of Medicine and Equipment for High Altitude Region,Faculty of High Altitude Military Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China;Department of Pathophysiology,Faculty of High Altitude Military Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China;Key Laboratory of Extreme Environmental Medicine of Ministry of Education,Faculty of High Altitude Military Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China;Key Laboratory of High Altitude Medicine of PLA,Faculty of High Altitude Military Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]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,重庆400038 [2]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,重庆400038 [3]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,重庆400038 [4]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,重庆400038

出　　处：《第三军医大学学报》2021年第4期295-302,共8页Journal of Third Military Medical University

基　　金：十二五军队重大项目(AWS16J023)。

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%O2缺氧处理HPASMCs分为3组:常氧组、缺氧24 h组、缺氧48 h组(n=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(n=3),干扰SOCS3表达分为3组:si-SOCS3-NC组、si-SOCS3-1组、si-SOCS3-2组(n=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(P<0.01),不仅能诱导HPASMCs增殖(P<0.05),还能显著上调p-STAT3、PCNA的表达(P<0.05)。在常氧条件下,干扰SOX6或SOCS3可显著增强HPASMCs的增殖(P<0.05),细胞中p-STAT3、PCNA的表达也显著升高(P<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(P<0.01),并显著降低p-STAT3、PCNA的表达(P<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。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% O2for 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.(3)The 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.(4)CCK-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(P<0.01), induced the proliferation of HPASMCs and up-regulated the levels of p-STAT3 and PCNA(P<0.05). Under normoxia condition, the reduction of SOX6 or SOCS3 not only significantly increased the proliferation of HPASMCs(P<0.05) butalso the levels of p-STAT3 and PCNA(P<0.01). Under hypoxia, overexpression of SOX6 obviously suppressed hypoxia-induced proliferation and the expression levels of p-STAT3 and PCNA(P<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：SOX6 SOCS3 STAT3 肺动脉平滑肌细胞 缺氧 增殖 

分 类 号：R322.121[医药卫生—人体解剖和组织胚胎学] R363.21[医药卫生—基础医学]