Mechanical strain and dexamethasone selectively increase surfactant protein C and tropoelastin gene expression

Abstract

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.

Mechanical Ventilation Effect on Surfactant Content, Function, and Lung Compliance in the Newborn Rat

“…Previous in vitro and in vivo studies have shown that phasic alveolar stretch induced by different tidal volumes is an important mediator of LA conversion. In addition, mechanical stretch induces expression of SP-C in fetal lung cells (30).…”

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems

“…Mechanical stresses have been shown to play an important role in regulating various functions of pulmonary epithelial cells such as growth (1)(2)(3), apoptosis (4-7), migration (8,9), surfactant metabolism (1,6,(10)(11)(12), synthesis of extracellular matrix proteins (11,13), and transport of fluids and ions (12,14,15). Disruption of the local mechanical environment of the pulmonary epithelium often elicits abnormal cellular responses and can contribute to the pathogenesis and progression of various respiratory diseases (4,5,(15)(16)(17)(18)(19)(20).…”

Mechanical ventilation and elastic fiber assembly

“…The pathogenesis of CLD is linked to structural lung immaturity and impaired alveolarization, with elevated levels of disorganized lung elastin (5,15,16). Elastin production is known to be markedly upregulated by strain or stretching of the cell matrix (9,14). Lung histology of infants who have died with CLD shows thickened, tortuous, and irregular distribution of elastic fibers in the walls of distal air spaces, with reduced septation and fewer alveoli (5, 16).…”