Aim: To explore the relationship between expression of signal transduction and activators of transcription 3 (STAT3) gene and proliferation of rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxia conditions.
Methods: After primarily cultured rat PASMCs was treated with AG490 and then exposed to hypoxia, the tyrosine-phosphorylated STAT3 protein were detected at 2 h, 6 h, 12 h, 16 h, 24 h of exposure to hypoxia by semi-quantitive RT-PCR (sqRT-PCR) and Western blot respectively. The expression of c-myc mRNA was analyzed by sqRT-PCR. 3H-TdR incorporation was used to detect the cell proliferation.
Results: The level of tyrosine-phosphorylated STAT3 increased at 6 h and peaked at 12 h. The expression of c-myc mRNA increased after 2 h of hypoxia and reached maximal level at 4 h, then declined at 6 h and to the basal levels at 12 h. With the prolonging of hypoxia time, 3H-TdR incorporation in PASMC under hypoxia conditions was significantly higher. AG490 inhibited proliferation of PASMCs by preventing STAT3 tyrosine phosphorylation and the expression of c-myc under hypoxia conditions.
Conclusion: (1) The activation of STAT3 and c-myc gene might play an important role in the early stage of hypoxia-induced PASMCs proliferation. (2) STAT3 upregulated the expression of c-myc during the proliferation of PASMCs induced by hypoxia.