Mechanical strain and dexamethasone selectively increase surfactant protein C and tropoelastin gene expression.
Physical forces derived from fetal breathing movements and hormones such as glucocorticoids are implicated in regulating fetal lung development. To elucidate whether the different signaling pathways activated by physical and hormonal factors are integrated and coordinated at the cellular and transcriptional levels, organotypic cultures of mixed fetal rat lung cells were subjected to static culture or mechanical strain in the presence and absence of dexamethasone. Tropoelastin and collagen type I were used as marker genes for fibroblasts, whereas surfactant protein (SP) A and SP-C were used as marker genes for distal epithelial cells. Mechanical strain, but not dexamethasone, significantly increased SP-C mRNA expression. Tropoelastin mRNA expression was upregulated by both mechanical strain and dexamethasone. No additive or synergistic effect was observed when cells were subjected to mechanical stretch in the presence of dexamethasone. Neither mechanical strain nor dexamethasone alone or in combination had any significant effect on the expression of SP-A mRNA. Dexamethasone decreased collagen type I mRNA expression, whereas mechanical strain had no effect. The increases in tropoelastin and SP-C mRNA levels induced by mechanical strain and/or dexamethasone were accompanied by increases in their heterogeneous nuclear RNA. In addition, the stretch- and glucocorticoid-induced alterations in tropoelastin and SP-C mRNA expression were abrogated with 10 microg/ml actinomycin D. These findings suggest that tropoelastin and SP-C genes are selectively stimulated by physical and/or hormonal factors at the transcriptional level in fetal lung fibroblasts and distal epithelial cells, respectively.
Nakamura
T
T
Lung Biology Program, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
Liu
M
M
Mourgeon
E
E
Slutsky
A
A
Post
M
M
D000818:Animals; D003094:Collagen / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005333:Fetus / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D008168:Lung / Q000196:embryology* / Q000502:physiology*; D009924:Organ Culture Techniques; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012332:RNA, Heterogeneous Nuclear / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013314:Stress, Mechanical; D014158:Transcription, Genetic / Q000502:physiology; D014333:Tropoelastin / Q000235:genetics*
D005938:Glucocorticoids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D014333:Tropoelastin; D003907:Dexamethasone; D003094:Collagen