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Limited choice for prophylactic treatment warrants effective therapy against <jats:styled-content style=\"fixed-case\">HAPE<\/jats:styled-content>. Keratinocyte growth factor\u20102 (<jats:styled-content style=\"fixed-case\">KGF<\/jats:styled-content>\u20102) has shown efficiency in preventing alveolar epithelial cell <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damages <jats:italic>in vitro<\/jats:italic>. In the current study, the effects of <jats:styled-content style=\"fixed-case\">KGF<\/jats:styled-content>\u20102 intratracheal instillation on mortality, lung liquid balance and lung histology were evaluated in our previously developed rat model of <jats:styled-content style=\"fixed-case\">HAPE<\/jats:styled-content>. We found that pre\u2010treatment with <jats:styled-content style=\"fixed-case\">KGF<\/jats:styled-content>\u20102 (5\u00a0mg\/kg) significantly decreased mortality, improved oxygenation and reduced lung wet\u2010to\u2010dry weight ratio by preventing alveolar\u2010capillary barrier disruption demonstrated by histological examination and increasing alveolar fluid clearance up to 150%. In addition, <jats:styled-content style=\"fixed-case\">KGF<\/jats:styled-content>\u20102 significantly inhibited decrease of transendothelial permeability after exposure to hypoxia, accompanied by a 10\u2010fold increase of Akt activity and inhibited apoptosis in human pulmonary microvascular endothelial cells, demonstrating attenuated endothelial apoptosis might contribute to reduction of endothelial permeability. These results showed the efficacy of <jats:styled-content style=\"fixed-case\">KGF<\/jats:styled-content>\u20102 on inhibition of endothelial cell apoptosis, preservation of alveolar\u2010capillary barrier integrity and promotion of pulmonary oedema absorption in <jats:styled-content style=\"fixed-case\">HAPE<\/jats:styled-content>. Thus, <jats:styled-content style=\"fixed-case\">KGF<\/jats:styled-content>\u20102 may represent a potential drug candidate for the prevention of <jats:styled-content style=\"fixed-case\">HAPE<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2012.01588.x","type":"journal-article","created":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T09:25:17Z","timestamp":1336555517000},"page":"3074-3084","source":"Crossref","is-referenced-by-count":32,"title":["<scp>KGF<\/scp>\u20102 targets alveolar epithelia and capillary endothelia to reduce high altitude pulmonary oedema in rats"],"prefix":"10.1111","volume":"16","author":[{"given":"Jun","family":"She","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Goolaerts","sequence":"additional","affiliation":[{"name":"Facult\u00e9 Bichat Universit\u00e9 Paris 7 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