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Vitamin D Receptor Deletion Leads to an Asthma Phenotype
Author(s) -
Rehan Virender K.,
Li Yishi,
Kovacs Christopher,
Torday John
Publication year - 2011
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.25.1_supplement.660.2
Subject(s) - wnt signaling pathway , signal transduction , biology , phenotype , receptor , endocrinology , medicine , pathogenesis , blot , microbiology and biotechnology , immunology , genetics , gene
Background Despite strong epidemiological association between the perinatal vitamin D (VD) deficiency and childhood asthma, the mechanistic link between the two is not established. We aimed to determine the effect of VD receptor deletion on the key markers of lung maturation. Methods The lungs of wild type and VD receptor null mutant mice (C57BL6) were examined at 2 and 7 weeks postnatally for morphometry and markers of lung maturation by RT‐PCR, Western blotting, and immunohistochemistry (IHC). Using the Affymetrix Mouse Genome 430 2.0 array, the transcriptional profile of the lungs from the two groups at 7 weeks of age was also examined. Results Both by Western analysis and IHC, there was down‐regulation of the intermediates for PTHrP/PPARγ signaling, a key signaling pathway for lung maturation. In contrast, there was up‐regulation of Wnt signaling, a key pathway in the pathogenesis of asthma. Self‐Organizing Map cluster analysis corroborated these data by showing up‐regulation of the Wnt signaling pathway, and down‐regulation of the PTHrP/PPARγ signaling pathway in VD receptor null mice compared to WT mice. Conclusions Altered VD signaling leads to down‐regulation of homeostatic PTHrP/PPARγ signaling, and up‐regulation of Wnt signaling, predisposing to a myogenic pulmonary phenotype that is consistent with the propensity to asthma in VD deficiency (Grants: HL75405, HD51857, HD58948).