JAK-STAT signaling pathway in pulmonary arterial smooth muscle cells is activated by hypoxia.
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.
Wang
Guan-Song
GS
Institute of Respiratory Diseases, Xinqiao Hospital, 2 Xinqioa Street, Chongqing 400037, China.
Qian
Gui-Sheng
GS
Zhou
De-Shan
DS
Zhao
Ji-Qing
JQ
D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; C507936:Jak3 protein, rat; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D011505:Protein-Tyrosine Kinases; C507906:Jak1 protein, rat; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D019950:Mitogen-Activated Protein Kinase 1