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Mice Deficient in the Src Family Tyrosine Kinase yes are Protected from Hyperoxia‐Induced Lung Injury
Author(s) -
Nelin Leif,
Jin Yi,
Liu Yusen,
Chicoine Louis,
Chen Bernadette
Publication year - 2015
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.29.1_supplement.1017.3
Subject(s) - hyperoxia , fyn , ards , endocrinology , medicine , lung , apoptosis , microbiology and biotechnology , tyrosine kinase , biology , chemistry , biochemistry , receptor
Endothelial cell apoptosis is an early event in the development of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) and bronchopulmonary dysplasia (BPD). In pulmonary endothelial cell culture studies we found that the Src family tyrosine kinase (STK) yes activated caspase 3, while the STK fyn inhibited caspase 3 activation. Therefore, we tested the hypothesis that mice deficient in yes will be protected from hyperoxia‐induced lung injury. Wild‐type (WT), yes ‐/‐ and fyn ‐/‐ mice were exposed to >95% O 2 or room air for 48 hours. The animals were weighed and lung tissue harvested. The left lungs were used for determination of wet‐to‐dry weight ratios (W/D) and the right lungs for western blotting for p21 and cleaved caspase‐3, as well as qPCR for cationic amino acid transporter (CAT)‐1, CAT‐2, arginase1, arginase2, inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX2). In the mice exposed to hyperoxia, yes ‐/‐ mice lost less body weight than did the WT or fyn ‐/‐ mice. Furthermore, yes ‐/‐ mice also had significantly lower lung W/D than did the WT or fyn ‐/‐ mice. Cleaved caspase‐3 protein levels were lower in the yes ‐/‐ mice than in WT and fyn ‐/‐ mice, while fyn ‐/‐ mice showed higher p21 protein levels than did WT and yes ‐/‐ mice. Following hyperoxia exposure the mRNA levels for CAT‐1, arginase 2, and iNOS were lower in the yes ‐/‐ mice than in WT and fyn ‐/‐ mice. Our results demonstrate that yes is an important positive regulator of hyperoxia‐induced iNOS expression and apoptosis in a mouse model of inflammatory lung disease.