Glucocorticoids influence versican and chondroitin sulphate proteoglycan levels in the fetal sheep lung

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Article number155
Number of pages12
JournalRespiratory Research
Volume19
Issue number1
DOIs
Publication statusPublished - 20 Aug 2018

Keywords

  • Adrenalectomy
  • Betamethasone
  • Cortisol
  • Extracellular matrix
  • Lung development

Cite this

@article{89001bb19d2244269e7af95d5068c7cc,
title = "Glucocorticoids influence versican and chondroitin sulphate proteoglycan levels in the fetal sheep lung",
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.",
keywords = "Adrenalectomy, Betamethasone, Cortisol, Extracellular matrix, Lung development",
author = "McDougall, {Annie Rene Alison} and Fosang, {Amanda J} and Jessica Faggian and Wallace, {Megan Jane} and Crossley, {Kelly Jane} and Cole, {Timothy James} and Hooper, {Stuart Brian}",
year = "2018",
month = "8",
day = "20",
doi = "10.1186/s12931-018-0854-4",
language = "English",
volume = "19",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",

}

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 journalArticleResearchpeer-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 -