Abstract
Background: Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Methods: Lung tissue was collected from 1) fetal sheep at 131±0.1days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2×11.4mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Results: Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4±0.7AU, compared with saline-infused fetuses (18.9±0.7AU: p=0.04) but did not significantly alter the level of versican or chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2±2.2AU), compared with sham-operated fetuses (17.8±2.0AU; p=0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2±0.9AU, 24.9±1.4AU and 23.2±1.0AU, respectively), compared with saline-exposed fetuses (24.3±0.4AU, p=0.0004; 33.3±0.6AU, p=0.0003; 29.8±1.3AU, 0.03, respectively). Conclusions: These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol.
| Original language | English |
|---|---|
| Article number | 155 |
| Number of pages | 12 |
| Journal | Respiratory Research |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 20 Aug 2018 |
Keywords
- Adrenalectomy
- Betamethasone
- Cortisol
- Extracellular matrix
- Lung development
Cite this
}
Glucocorticoids influence versican and chondroitin sulphate proteoglycan levels in the fetal sheep lung. / McDougall, Annie Rene Alison; Fosang, Amanda J; Faggian, Jessica; Wallace, Megan Jane; Crossley, Kelly Jane; Cole, Timothy James; Hooper, Stuart Brian.
In: Respiratory Research, Vol. 19, No. 1, 155, 20.08.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Glucocorticoids influence versican and chondroitin sulphate proteoglycan levels in the fetal sheep lung
AU - McDougall, Annie Rene Alison
AU - Fosang, Amanda J
AU - Faggian, Jessica
AU - Wallace, Megan Jane
AU - Crossley, Kelly Jane
AU - Cole, Timothy James
AU - Hooper, Stuart Brian
PY - 2018/8/20
Y1 - 2018/8/20
N2 - Background: Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Methods: Lung tissue was collected from 1) fetal sheep at 131±0.1days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2×11.4mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Results: Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4±0.7AU, compared with saline-infused fetuses (18.9±0.7AU: p=0.04) but did not significantly alter the level of versican or chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2±2.2AU), compared with sham-operated fetuses (17.8±2.0AU; p=0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2±0.9AU, 24.9±1.4AU and 23.2±1.0AU, respectively), compared with saline-exposed fetuses (24.3±0.4AU, p=0.0004; 33.3±0.6AU, p=0.0003; 29.8±1.3AU, 0.03, respectively). Conclusions: These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol.
AB - Background: Prenatal glucocorticoid treatment decreases alveolar tissue volumes and facilitates fetal lung maturation, however the mechanisms responsible are largely unknown. This study examines whether changes in versican levels or sulphation patterns of chondroitin sulphate (CS) side chains, are associated with glucocorticoid-induced reductions in peri-alveolar tissue volumes. Methods: Lung tissue was collected from 1) fetal sheep at 131±0.1days gestational age (GA) infused with cortisol (122-131d GA) to prematurely induce a pre-parturient-like rise in circulating cortisol, 2) fetal sheep at 143d GA bilaterally adrenalectomised (ADX) at 112d GA to remove endogenous cortisol and 3) fetal sheep at 124d GA in which bolus doses (2×11.4mg) of betamethasone were administered to the pregnant ewe. The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry (IHC). Fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Results: Cortisol infusion significantly decreased chondrotin-6-sulphate levels (C-6-S) to 16.4±0.7AU, compared with saline-infused fetuses (18.9±0.7AU: p=0.04) but did not significantly alter the level of versican or chondroitin-4-sulphate (C-4-S). ADX significantly increased the level of C-4-S (28.2±2.2AU), compared with sham-operated fetuses (17.8±2.0AU; p=0.006) without altering versican or C-6-S levels. Betamethasone significantly decreased versican, C-4-S and C-6-S in the fetal sheep lung (19.2±0.9AU, 24.9±1.4AU and 23.2±1.0AU, respectively), compared with saline-exposed fetuses (24.3±0.4AU, p=0.0004; 33.3±0.6AU, p=0.0003; 29.8±1.3AU, 0.03, respectively). Conclusions: These results indicate that glucocorticoids alter versican levels and CS side chain microstructure in alveolar lung tissue. Betamethasone appears to have a greater impact on versican and CS side chains than cortisol.
KW - Adrenalectomy
KW - Betamethasone
KW - Cortisol
KW - Extracellular matrix
KW - Lung development
UR - http://www.scopus.com/inward/record.url?scp=85052087414&partnerID=8YFLogxK
U2 - 10.1186/s12931-018-0854-4
DO - 10.1186/s12931-018-0854-4
M3 - Article
VL - 19
JO - Respiratory Research
JF - Respiratory Research
SN - 1465-9921
IS - 1
M1 - 155
ER -