Wang Guan-Song, Qian Gui-Sheng, Zhou De-Shan, Zhao Ji-Qing
Institute of Respiratory Diseases, Xinqiao Hospital, 2 Xinqioa Street, Chongqing 400037, China.
Cell Biol Int. 2005 Jul;29(7):598-603. doi: 10.1016/j.cellbi.2005.03.014.
Pulmonary arterial smooth muscle cells (PASMC) were divided into a normoxic group (N), 2, 8 and 12 h hypoxic groups (H2, H8 and H12) and an AG490 plus 8 h hypoxic group (AG490). The expression of JAK1, JAK2, JAK3 and TYK2 mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). STAT1 and STAT3 protein expressions were determined by Western blotting. The results showed that the levels of JAK1, JAK2 and JAK3 mRNA did not change significantly in the N group but were increased after 2 h exposure to hypoxia. JAK1, JAK2 and JAK3 mRNA expressions peaked at 8 h. It decreased at 12 h but remained above those in the N group. TYK2 mRNA was not found in either hypoxic or normal PASMC. The phospho-STAT1 and -STAT3 protein levels increased after 2 h exposure to hypoxia. They were about 2.8 and 4.1 times the N group, respectively, after 8 h. They decreased at 12 h but remained above those in the N group. AG490 inhibited phospho-STAT3 protein expression by about 25.5% at 8 h but did not block the expression of phospho-STAT1 protein. These findings suggest that hypoxia induces the expression of JAK1, JAK2, JAK3 and phospho-STAT1 and -STAT3 in PASMC. Hypoxia activates the JAKs-STATs signaling pathway, which may participate in the pathogenesis of hypoxic PASMC injury.
肺动脉平滑肌细胞（PASMC）被分为常氧组（N）、2小时、8小时和12小时缺氧组（H2、H8和H12）以及AG490加8小时缺氧组（AG490）。通过逆转录-聚合酶链反应（RT-PCR）分析JAK1、JAK2、JAK3和TYK2 mRNA的表达。通过蛋白质印迹法测定STAT1和STAT3蛋白表达。结果显示，JAK1、JAK2和JAK3 mRNA水平在N组中无明显变化，但在缺氧2小时后升高。JAK1、JAK2和JAK3 mRNA表达在8小时达到峰值。在12小时时下降，但仍高于N组。在缺氧或正常的PASMC中均未发现TYK2 mRNA。缺氧2小时后磷酸化STAT1和-STAT3蛋白水平升高。8小时后，它们分别约为N组的2.8倍和4.1倍。在12小时时下降，但仍高于N组。AG490在8小时时抑制磷酸化STAT3蛋白表达约25.5%，但不阻断磷酸化STAT1蛋白的表达。这些发现表明，缺氧诱导PASMC中JAK1、JAK2、JAK3以及磷酸化STAT1和-STAT3的表达。缺氧激活JAKs-STATs信号通路，这可能参与缺氧性PASMC损伤的发病机制。
