1alpha,25(OH)2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipofibroblast apoptosis.
Am J Physiol Lung Cell Mol Physiol
; 297(3): L496-505, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19574420
ABSTRACT
Although alveolar wall thinning has been attributed to apoptosis of interstitial lung lipofibroblasts (LFs), the underlying molecular mechanism(s) remains unknown. Although the physiological vitamin D steroid hormone 1alpha,25(OH)(2)D(3) (1,25D) has been suggested as a local paracrine/autocrine effector of fetal lung maturation and is known to affect fibroblast apoptosis, its effects on LF apoptosis are unknown. We determined the role of 1,25D and its metabolite, C-3-epimer (3-epi-1,25D), on LF and alveolar type II (ATII) cell differentiation, proliferation, and apoptosis. Embryonic day 19 Sprague-Dawley fetal rat lung LFs and ATII cells were treated with 1,25D or 3-epi-1,25D (1 x 10(-10) to 1 x 10(-8) M) for 24 h, and cell proliferation, apoptosis, and differentiation were assessed. Both 1,25D and 3-epi-1,25D exhibited dose-dependent increases in expression of the key homeostatic epithelial-mesenchymal differentiation markers, increased LF and ATII cell proliferation, and decreased apoptosis. Furthermore, rat pups administered 1,25D from postnatal days 0 to 14 showed increased expressions of key LF and ATII cell differentiation markers, increased Bcl-2-to-Bax ratio as an index of decreased spontaneous alveolar LF and ATII cell apoptosis, increased alveolar count, and a paradoxical increase in septal thickness. We conclude that spatial- and temporal-specific actions of vitamin D play a critical role in perinatal lung maturation by stimulating key alveolar epithelial-mesenchymal interactions and by modulating LF proliferation/apoptosis. These data not only provide the biological rationale for the presence of an alveolar vitamin D paracrine system, but also provide the first integrated molecular mechanism for increased surfactant synthesis and alveolar septal thinning during perinatal lung maturation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alvéolos Pulmonares
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Calcitriol
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Comunicação Celular
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Apoptose
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Células Epiteliais
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Fibroblastos
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Mesoderma
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos