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Epithelial Cell PPARγ Deficiency Results in Abnormalities in Lung Structure and Function
Author(s) -
Mariani Thomas J,
Ingenito Ed,
Tsai Larry,
Starcher Barry,
Simon Dawn M.
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.a1341-a
Subject(s) - elastin , lung , pulmonary surfactant , endocrinology , elastic recoil , receptor , medicine , parenchyma , pathology , chemistry , alveolar epithelium , biology , biochemistry
Peroxisome proliferator‐activated receptor (PPAR)‐γ is a nuclear hormone receptor that regulates gene expression, cell proliferation and differentiation. We previously described mice with conditional PPARγ deficiency within the conducting airway epithelium. These conditionally targeted mice develop airspace enlargement coincident with alveolarization that is not progressive with ageing. Measurement of lung mechanics in these animals revealed decreased tissue resistance and increased lung volumes. Analysis of air‐saline filled pressure volume profiles demonstrated loss of elastic recoil. No significant differences in surfactant quantity (phospholipids content) or function (surfactometry) were observed between targeted animals and littermate controls. Elastin and collagen histochemistry and biochemistry also showed no gross changes between targeted and control animals. We analyzed parenchymal structure by measuring the distribution of alveoli (defined as airspaces of 250–2000 _m2) and alveolar ducts (>5000 _m2). At 8 weeks of age, there were fewer alveoli (mean number of 126 vs 154, p<0.001) and more alveolar ducts (mean number of 11.1 vs 8.4, p<0.001). Additionally, the alveolar ducts were larger (mean size of 10,274 _m2 vs 8,658 _m2, p<0.001) in the targeted animals. Radial alveolar counts were reduced in the targeted animals (mean number of 8.2 vs. 9.9, p=0.045). These data suggest that the functional abnormalities, including loss of recoil contributed by the air‐liquid interface are secondary to altered force transmission due to differences in structure of the alveolar duct, rather than changes in surfactant function or elastin or collagen content. Supported by CF Foundation and NIH HL71885