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Activation of signal transducer and activator of transcription (STAT) 3 in hypoxia‐induced pulmonary hypertension
Author(s) -
Mathew Rajamma,
Huang Jing,
Zhao Xiangmin,
Olson Susan,
Gewitz Michael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1435-b
Subject(s) - enos , stat3 , stat protein , hypoxia (environmental) , caveolin 1 , pulmonary hypertension , in vivo , biology , microbiology and biotechnology , medicine , chemistry , signal transduction , endocrinology , nitric oxide , nitric oxide synthase , oxygen , organic chemistry
We have previously shown that monocrotaline (MCT)‐induced pulmonary hypertension (PH) is associated with a reduction in caveolin‐1 expression and reciprocal activation of STAT3 (PY‐STAT3), a proproliferative transcription factor. Caveolin‐1 negatively regulates cell proliferation and is an inhibitor of STAT3 activation. Since hypoxia leads to a tight caveolin‐1/eNOS complex formation, we hypothesized that this complex may modulate caveolin‐1‐related signaling molecule (PY‐STAT3) involved in cell proliferation. Rats were subjected to hypobaric hypoxia (50 Kp) and examined at 48h, 1 and 2 wks. In addition, bovine pulmonary artery endothelial cells (BPAEC) were subjected to hypoxia (5% O 2 ) for 24 hrs. Progressive PH and RVH were observed in rats exposed to hypoxia. eNOS expression was increased in the hypoxia groups (1.6‐2 fold) compared with the controls. Progressive activation of PY‐STAT3 was observed in the hypoxia‐exposed rat lungs (1.4‐4 fold). Hypoxia‐exposed BPAEC revealed alterations in eNOS/caveolin‐1 interrelationship and activation of PY‐STAT3. The expression of caveolin‐1 was not significantly altered in in‐vivo or in‐vitro model. We conclude that the hypoxia‐induced alterations in eNOS/caveolin‐1 interrelationship may influence inhibitory effects of caveolin‐1 on cell proliferation and that the activation of PY‐STAT3 plays a pivotal role in the pathogenesis of PH.