Alterations in lung expansion affect surfactant protein A, B, and C mRNA levels in fetal sheep

Lines, Andrea; Nardo, Laura; Phillips, Ian D.; Possmayer, Fred; Hooper, Stuart B.

doi:10.1152/ajplung.1999.276.2.l239

Cited by 44 publications

(68 citation statements)

References 19 publications

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“…The current studies show that decreased distension not only retards lung growth but also inhibits differentiation of type I cells. Previous studies have shown that increased lung distension in fetal sheep accelerates lung growth and decreases numbers of type II cells and surfactant (2,11,18,28,32,37). The cellular mechanisms involved in the responses to changes in distension of the fetal lung have not been defined.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, other investigators have studied tracheal ligation in fetal sheep and have confirmed that an increase in lung distension results in a lower number of type II cells (6,11,37) and a higher percentage of type I cells (18). Tracheal ligation also results in lower concentrations in the lung of surfactant protein (SP)-A and saturated phosphatidylcholine (SatPC), the major surface-active lipid in pulmonary surfactant (28), as well as mRNA for SP-A, -B, and -C (32). Conversely, transection of the cervical spinal cord (which abolishes fetal breathing movements) produces hypoplastic lungs with higher concentrations of SP-A and SatPC (28).…”

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confidence: 94%

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Effects of oligohydramnios on lung growth and maturation in the fetal rat

Kitterman

Chapin

Vanderbilt

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Oligohydramnios (OH) retards fetal lung growth by producing less lung distension than normal. To examine effects of decreased distension on fetal lung development, we produced OH in rats by puncture of uterus and fetal membranes at 16 days of gestation; fetuses were delivered at 21 or 22 days of gestation. Controls were position-matched littermates in the opposite uterine horn. OH lungs had lower weights and less DNA, protein, and water, but no differences in saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP-A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used RTI 40 and RTII70, proteins specific in lung to luminal surfaces of alveolar type I and II cells, respectively. At 22 days of gestation, OH lungs had less RTI40 mRNA (P Ͻ 0.05) and protein (P Ͻ 0.001), but RTII70 did not differ from controls. With OH, type I cells (in proportion to type II cells) covered less distal air space perimeter (P Ͻ 0.01). We conclude that OH, which retards lung growth, has little effect on surfactant and impedes formation of type I cells relative to type II cells. fetal lung development; lung distension; pulmonary epithelial differentiation; pulmonary hypoplasia; pulmonary surfactant IN LATE GESTATION, the fetal lung undergoes marked changes in preparation for the transition to extrauterine life. These changes include growth, enlargement of distal potential air spaces, thinning of the septa, maturation of the surfactant system, and differentiation of distal pulmonary epithelium into mature alveolar type I and type II cells. Several studies have shown that fetal lung growth is controlled primarily by mechanical factors, especially distension of the lung (for reviews, see Refs. 26 and 29) and that maturation of the surfactant system is controlled primarily by endocrine factors (for reviews, see Refs. 3 and 48). In contrast, relatively little is known about factors that regulate differentiation of the alveolar epithelium.In 1977, Alcorn and associates (2) reported that tracheal ligation in fetal sheep, which increased lung distension, caused accelerated lung growth and a qualitative reduction in the number of alveolar type II cells; conversely, chronic drainage of tracheal fluid, which inhibited lung distension, retarded lung growth and increased the number of type II cells. However, they reported neither quantitative data for cell counts nor measurements of indicators of surfactant, which is produced by type II cells. Subsequently, other investigators have studied tracheal ligation in fetal sheep and have confirmed that an increase in lung distension results in a lower number of type II cells (6,11,37) and a higher percentage of type I cells (18). Tracheal ligation also results in lower concentrations in the lung of surfactant protein (SP)-A and saturated phosphatidylcholine (SatPC), the major surface-active lipid in pulmonary surfactant (28), as well as mRNA for SP-A, -B, and -C (32). Conversely, transection of the cervical spinal cord (which abolishes fetal breathing movemen...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

Effects of oligohydramnios on lung growth and maturation in the fetal rat

Kitterman

Chapin

Vanderbilt

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Versican mRNA levels in lung tissue were measured from fetal sheep and newborn lambs by Northern blot analysis, as previously described (18,19). Total RNA was extracted from lung tissue (40 g), denatured, and electrophoresed in a 0.8% agarose gel containing 2.2 M formaldehyde.…”

Section: Analytic Methodsmentioning

confidence: 99%

Changes in versican and chondroitin sulfate proteoglycans during structural development of the lung

Faggian¹,

Fosang²,

Zieba³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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We have examined whether changes in versican levels, or in the sulfation pattern of its chondroitin sulfate (CS) side chains, are associated with the reduction in perialveolar tissue volumes that characterize lung maturation in late-gestation fetal sheep. Lung tissue was collected from fetuses [90–142 days gestational age (GA)] and lambs (2 wk after term birth). The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry, whereas fluorophore-assisted carbohydrate electrophoresis was used to determine changes in CS sulfation patterns. Versican was the predominant CS-containing proteoglycan in the lung and decreased from 19.9 ± 2.7 arbitrary units at 90 days GA to 6.0 ± 0.5 arbitrary units at 142 days GA, in close association ( P < 0.05) with the reduction in tissue volumes (from 66.0 ± 4.6 to 25.3 ± 1.5% at 142 days); similar reductions occurred for both chondroitin-6-sulfate and chondroitin-4-sulfate CS side chains. Hyaluronic acid levels decreased from 3,168 ± 641 pmol/μg GAG at 90 days GA to 126 ± 9 pmol/μg GAG at 142 days GA, and the predominant sulfated disaccharide changed from Δ-di-6S at 90 days GA to Δ-di-4S at term. These data indicate that structural development of the lung is closely associated with marked changes in versican levels and the microstructure of CS side chains in perisaccular/alveolar lung tissue.

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“…Hence, one of our aims was to determine the effect of increased lung expansion on surfactant protein mRNA levels in the air-filled lungs of normal lambs. We hypothesized that the inverse relationship between increased lung expansion and surfactant protein gene expression, recently described in fetal sheep (5), persists in normal lambs after birth.…”

mentioning

confidence: 99%

“…The degree to which the fetal lungs are expanded by liquid not only determines the rate of lung tissue growth (3), but also profoundly influences the differentiated state of alveolar epithelial cells (4). As a result, there is a strong relationship between the degree of fetal lung expansion and the expression of the surfactant proteins, SP-A, SP-B, and SP-C (5)(6)(7)(8). Increases in fetal lung expansion rapidly (within 2 days) reduce SP-A, SP-B, and SP-C mRNA levels (5), whereas continuous deflation of the fetal lung increases SP-C mRNA levels (5) and SP-A levels (7).…”

mentioning

confidence: 99%