Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium

Abstract

Rat fetal lung is a target tissue for 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25 (OH)2 D3]. We have identified the cells that respond to the hormone and tested the hypothesis that the lung is also a source of 1 alpha,25(OH)2D3. We found that 1) at the end of pregnancy (days 20-21) alveolar type II cells (ATII) bore 1 alpha,25(OH)2D3 receptors and responded to the hormone. Incubating these cells with 10(-9) M 1 alpha,25(OH)2D3 for 48 h stimulated the synthesis (87.3 +/- 9.1%) and release (61.7 +/- 6.1%) of disaturated phosphatidylcholine; 2) EB-1213, a 1 alpha,25(OH)2D3 analogue with low calcemic activity, had similar effects on ATII; 3) neither fetal lung fibroblasts nor neonatal ATII (day 2 postpartum) expressed 1 alpha,25(OH)2D3 receptors; and 4) in contrast, fetal lung fibroblasts taken on days 19-22 of gestation converted [3H]25(OH)D3 to [3H]1 alpha,25(OH)2D3, whereas ATII and skin fibroblasts did not. These findings suggest that 1 alpha,25(OH)2D3 is a local mediator of epithelial-mesenchymal cell interactions in the developing rat lung and that 1 alpha,25(OH)2D3 or EB-1213 might be therapeutically useful in treating the respiratory distress syndrome of premature neonates.

Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia

“…ETX-exposed rat pups have marked reductions in alveolarization, vascular growth, and pulmonary hypertension, which mimic features of human BPD (11,42). In addition, past studies suggest that vit D modulates fetal rat lung maturation and may be protective for respiratory distress syndrome in preterm neonates (35). Vit D also inhibits lung fibroblast proliferation and myofibroblast transdifferentiation in an adult model of lung fibrosis (39).…”

“…Vit D treatment attenuates inflammation in experimental autoimmune diseases and modulates cytokine production by vascular endothelial cells and human decidual cells (20,49). Importantly, vit D may contribute to normal development of the lung (35). Maternal vit D deficiency is associated with an increased risk for wheezing episodes during early childhood (46) and has also been linked with systemic vascular endothelial dysfunction, systemic hypertension, and an increased risk for cardiovascular disease (31,43).…”

The Nuclear Vitamin D Receptor: Biological and Molecular Regulatory Properties Revealed

“…(67) In some neurons, analogous to the antiapoptotic effect of calbindin-D 28k in lymphocytes, (68) the induction of calbindins by 1,25(OH) 2 D 3 may protect against cell death in the face of repetitive calcium transients, (69) and in fact the expression of calbindin-D 28k mRNA is decreased in the hippocampus of Alzheimer's patients as assessed by in situ hybridization. (70,71) Taken together, these observations not only imply a modulatory role for VDR in neural cell growth and differentiation but also intimate a possible role for 1,25(OH) 2 57) suppression of ␥-interferon (202) and IL-1 through IL-6 (53,159,203) Central nervous system dorsal root ganglia, (204) glial cells, and hippocampus (70,107) production of NGF, (65,66,205) neurotrophin-3, (64) and leukemia inhibitory factor (63) Epithelium epidermal skin/keratinocyte (206) differentiation (17,211) hair follicle (207) differentiation (16,17,212) female reproductive tract (208) uterine development (16) mammary (108) 2 cell growth (213) prostate (209) 2 cell growth (173) colon (210) 2 cell growth (170,214) lung (108) surfactant (215) Endocrine system thyrotrope (216) TRH receptor (218) thyroid (108) 2...…”

Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma

“…V itamin D exerts many of its effects through contact with vitamin D receptors [1], which have been found in a variety of cells, including lung cells [2] and many cells of the immune system [3]. The finding that most tissues and cells in the body have vitamin receptors and that several possess the enzymatic apparatus to synthesise the active form 1,25-dihydroxyvitamin D from the primary vitamin D, 25-hydroxyvitamin D, has provided new insight into the role of this vitamin deficiency in several diseases [4], including asthma [5].…”