Regulation of human pulmonary surfactant protein gene expression by 1alpha,25-dihydroxyvitamin D3.
1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has been reported to stimulate lung maturity, alveolar type II cell differentiation, and pulmonary surfactant synthesis in rat lung. We hypothesized that 1,25(OH)(2)D(3) stimulates expression of surfactant protein-A (SP-A), SP-B, and SP-C in human fetal lung and type II cells. We found that immunoreactive vitamin D receptor was detectable in fetal lung tissue and type II cells only when incubated with 1,25(OH)(2)D(3). 1,25(OH)(2)D(3) significantly decreased SP-A mRNA in human fetal lung tissue but did not significantly decrease SP-A protein in the tissue. In type II cells, 1,25(OH)(2)D(3) alone had no significant effect on SP-A mRNA or protein levels but reduced SP-A mRNA and protein in a dose-dependent manner when the cells were incubated with cAMP. SP-A mRNA levels in NCI-H441 cells, a nonciliated bronchiolar epithelial (Clara) cell line, were decreased in a dose-dependent manner in the absence or presence of cAMP. 1,25(OH)(2)D(3) had no significant effect on SP-B mRNA levels in lung tissue but increased SP-B mRNA and protein levels in type II cells incubated in the absence or presence of cAMP. Expression of SP-C mRNA was unaffected by 1,25(OH)(2)D(3) in lung tissue incubated +/- cAMP. These results suggest that regulation of surfactant protein gene expression in human lung and type II cells by 1,25(OH)(2)D(3) is not coordinated; 1,25(OH)(2)D(3) decreases SP-A mRNA and protein levels in both fetal lung tissue and type II cells, increases SP-B mRNA and protein levels only in type II cells, and has no effect on SP-C mRNA levels.
Phokela
Sarabjit S
SS
Dept. of Pediatrics, The University of Texas Health Science Center, Houston, TX 77030, USA.
Peleg
Sara
S
Moya
Fernando R
FR
Alcorn
Joseph L
JL
D000230:Adenocarcinoma; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
C116441:2-methyl-1,25-dihydroxyvitamin D3; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D037661:Pulmonary Surfactant-Associated Proteins; D012333:RNA, Messenger; D014807:Vitamin D