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Impact of the epithelial HIF 2 alpha system on lung development
Author(s) -
Ahlbrecht Katrin,
Seay Ulrike,
Schmitz Judith,
Haberberger Rainer V.,
Kraus Rita Mittnacht,
Herold Susanne,
Breier Georg,
Keith Brian,
Simon Celeste,
Whitsett Jeffrey A.,
Grimminger Friedrich,
Seeger Werner,
Voswinckel Robert
Publication year - 2008
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.22.1_supplement.930.2
Subject(s) - lung , alpha (finance) , embryonic stem cell , epithelium , biology , embryogenesis , microbiology and biotechnology , regulator , pathology , medicine , embryo , gene , genetics , construct validity , nursing , patient satisfaction
During lung development endothelial Flk‐1 is a key regulator of blood vessel formation and regulated by HIF 2‐alpha. Hif 2‐alpha is highly expressed in the lung around late embryonic stages and birth. Beside the endothelial expression remarkable expression in alveolar epithelial cells has been shown. Loss of HIF 2‐alpha led to the infant respiratory distress syndrome which could be prevented by VEGF treatment. The aim of this study is to investigate the role of the HIF 2‐alpha and Flk‐1 system in pulmonary epithelial cells during lung development. Therefore we generated an inducible epithelial specific HIF 2‐alpha knock out using the Cre/lox system in combination with a SPCrtTA system. Expression studies on different stages of lung development in wild type mice and in isolated alveolar epithelial cells revealed Flk‐1 and Hif 2‐alpha expression in the epithelial system. Adult epithelial HIF 2‐alpha −/− mice induced from embryonic day 0 were viable without rough defects but showed a strong down regulation of Flk‐1 in the isolated AECs. Detailed morphometry studies and studies on different pathological stimuli are in progress and will give further information about the effect of epithelial HIF 2‐alpha ko on lung development and alveolar function.