Activation of PPARγ reverses a defect of surfactant synthesis in mice lacking two types of fatty acid binding protein

Christian Schachtrup, Stefan Malcharek, Jack J. Haitsma, Burkhard Lachmann, Yuji Owada, Bert Binas, Hisatake Kondo, Bernd Rüstow, Hans Joachim Galla, Friedrich Spener

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Lung surfactant is a lipid-protein-film covering the inner alveolar surface. We have previously shown that double knock-out (d-ko) mice lacking both the epidermal-type (E-) and the heart-type (H-) fatty acid binding protein (FABP) exhibit a defect of surfactant synthesis in alveolar type II cells that can be corrected by feeding pioglitazone, a drug that activates peroxisome proliferator-activated receptor gamma (PPARγ). Here, we demonstrate first that healthy surfactant at collapse pressure produces protrusions composed of bilayers but not folds, second that the d-ko effect profoundly perturbs lipid/hydrophobic protein composition, pressure-area isotherm, and structural organisation of the surfactant at nanoscale, parameters that are critical for the normal breathing cycle. In support of these data in vivo measurements of lung function reveal that maximum compliance in d-ko vs. wild-type mice is significantly reduced. Further, we show that the biophysical phenotype can be corrected substantially with pioglitazone. Finally, we show that d-ko alveolar cells up-regulate liver-type (L-) FABP, a member of the FABP family that we have previously shown to interact with PPARγ. Taken together, these data suggest that PPARγ agonists could be a tool to repair surfactant damage caused by dysfunctional alveolar lipid metabolism, and provide in vivo support for L-FABP aided signaling.

本文言語English
ページ(範囲)314-320
ページ数7
ジャーナルBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
1781
6-7
DOI
出版ステータスPublished - 2008 6

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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