Sneha K Taylor1, Reiko Sakurai1, Tokusho Sakurai1, Virender K Rehan2. 1. Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson Street, Torrance, CA, 90502, USA. 2. Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson Street, Torrance, CA, 90502, USA. vrehan@labiomed.org.
Abstract
INTRODUCTION: The physiologic vitamin D (VD), 1α,25(OH)2D3 (1,25D) is a local paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar type II cell and lipofibroblast proliferation and differentiation, parenterally administered 1,25D has been shown to enhance neonatal lung maturation; but due to the potential systemic side effects of the parenteral route, the translational value of these findings might be limited. To minimize the possibility of systemic toxicity, we examined the effects of VD on neonatal lung maturation, when delivered directly to lungs via nebulization. METHODS: One-day-old rat pups were administered three different doses of 1,25D and its physiologic precursor 25(OH)D (25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed for lung, kidneys, and blood collection to determine markers of lung maturation, and serum 25D and calcium levels. RESULTS: Compared to controls, nebulized 25D and 1,25D enhanced lung maturation as evidenced by the increased expression of markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARγ, C/EBPα), and endothelial (VEGF, FLK-1) differentiation, surfactant phospholipid synthesis, and lung morphology without any significant increases in serum 25D and calcium levels. CONCLUSIONS: Inhaled VD is a potentially safe and effective novel strategy to enhance neonatal lung maturation.
INTRODUCTION: The physiologic vitamin D (VD), 1α,25(OH)2D3 (1,25D) is a local paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar type II cell and lipofibroblast proliferation and differentiation, parenterally administered 1,25D has been shown to enhance neonatal lung maturation; but due to the potential systemic side effects of the parenteral route, the translational value of these findings might be limited. To minimize the possibility of systemic toxicity, we examined the effects of VD on neonatal lung maturation, when delivered directly to lungs via nebulization. METHODS: One-day-old rat pups were administered three different doses of 1,25D and its physiologic precursor 25(OH)D (25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed for lung, kidneys, and blood collection to determine markers of lung maturation, and serum 25D and calcium levels. RESULTS: Compared to controls, nebulized 25D and 1,25D enhanced lung maturation as evidenced by the increased expression of markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARγ, C/EBPα), and endothelial (VEGF, FLK-1) differentiation, surfactant phospholipid synthesis, and lung morphology without any significant increases in serum 25D and calcium levels. CONCLUSIONS: Inhaled VD is a potentially safe and effective novel strategy to enhance neonatal lung maturation.
Authors: Katie N Evans; Lisa Nguyen; Junny Chan; Barbara A Innes; Judith N Bulmer; Mark D Kilby; Martin Hewison Journal: Biol Reprod Date: 2006-09-06 Impact factor: 4.285
Authors: Virender K Rehan; John S Torday; Sara Peleg; Lynn Gennaro; Paul Vouros; James Padbury; D Sunita Rao; G Satyanarayana Reddy Journal: Mol Genet Metab Date: 2002-05 Impact factor: 4.797
Authors: R Sakurai; E Shin; S Fonseca; T Sakurai; A A Litonjua; S T Weiss; J S Torday; V K Rehan Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-07-02 Impact factor: 5.464
Authors: Carlos A Camargo; Sheryl L Rifas-Shiman; Augusto A Litonjua; Janet W Rich-Edwards; Scott T Weiss; Diane R Gold; Ken Kleinman; Matthew W Gillman Journal: Am J Clin Nutr Date: 2007-03 Impact factor: 7.045
Authors: Juan Fandiño; Laura Toba; Lucas C González-Matías; Yolanda Diz-Chaves; Federico Mallo Journal: Nutrients Date: 2019-11-23 Impact factor: 5.717