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

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% O2 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 (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.

Keywords

• sox6
• socs3
• stat3
• human pulmonary artery smooth cells
• hypoxia
• proliferation