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

2007 ◽  
Vol 293 (2) ◽  
pp. R784-R792 ◽  
Author(s):  
Jessica Faggian ◽  
Amanda J. Fosang ◽  
Malgorzata Zieba ◽  
Megan J. Wallace ◽  
Stuart B. Hooper
Keyword(s):  
Chondroitin Sulfate ◽  
Lung Tissue ◽  
Close Association ◽  
Late Gestation ◽  
Chondroitin Sulfate Proteoglycans ◽  
Side Chains ◽  
Structural Development ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Sulfation Pattern

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.

Prepartum maturation of the lung in fetal sheep: relation to cortisol

1981 ◽  
Vol 51 (2) ◽  
pp. 384-390 ◽  
Author(s):  
J. A. Kitterman ◽  
G. C. Liggins ◽  
G. A. Campos ◽  
J. A. Clements ◽  
C. S. Forster ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Fetal Lung ◽  
Lavage Fluid ◽  
Late Gestation ◽  
Morphological Development ◽  
Lung Maturation ◽  
Physiological Factor ◽  
Fetal Sheep ◽  
Wide Range ◽  
Fetal Lung Maturation

We studied the relationship of certain fetal and maternal hormones to indicators of lung maturation in 12 fetal lambs delivered at gestational ages (GA) of 123-149 days. Maternal estrogen, maternal progesterone, and fetal prolactin did not correlate with GA or the indicators of fetal lung maturation. Fetal cortisol (range 4-165 ng X ml-1) increased with advancing GA (r = 0.747, P less than 0.01). All of the following showed a wide range of late gestation and showed a significant positive correlation with fetal cortisol: lung volumes at 40 cmH2O and 10 cmH2O on the deflation during air pressure-volume studies; saturated phosphatidylcholine (SPC) in lung tissue and in lavage fluid expressed both as mg X g-1 of wet lung and as percent of total phospholipids (%PL); total SPC (lung tissue plus lavage fluid): and SPC in lavage fluid as percent of total SPC. Lung DNA correlated inversely with GA and cortisol. All variables (except lavage fluid SPC as %PL) correlated more closely with cortisol than GA. Morphological development of lung was also related more closely to cortisol than GA. These results suggest that functional lung maturity is attained late in gestation and that endogenous cortisol is an important physiological factor in control of fetal lung maturation.

scholarly journals Chondroitin Sulfate Proteoglycans: Structure-Function Relationship with Implication in Neural Development and Brain Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Speranta Avram ◽  
Sergey Shaposhnikov ◽  
Catalin Buiu ◽  
Maria Mernea
Keyword(s):  
Nervous System ◽  
Chondroitin Sulfate ◽  
Neural Development ◽  
Genetic Disorders ◽  
Quantitative Structure Activity Relationship ◽  
Chondroitin Sulfate Proteoglycans ◽  
Side Chains ◽  
Health State ◽  
Brain Disorders ◽  
Extracellular Matrix Components

Chondroitin sulfate proteoglycans (CSPGs) are extracellular matrix components that contain two structural parts with distinct functions: a protein core and glycosaminoglycan (GAG) side chains. CSPGs are known to be involved in important cell processes like cell adhesion and growth, receptor binding, or cell migration. It is recognized that the presence of CSPGs is critical in neuronal growth mechanisms including axon guidance following injury of nervous system components such as spinal cord and brain. CSPGs are upregulated in the central nervous system after injury and participate in the inhibition of axon regeneration mainly through their GAG side chains. Recently, it was shown that some CSPGs members like aggrecan, versican, and neurocan were strongly involved in brain disorders like bipolar disorder (BD), schizophrenia, and ADHD. In this paper, we present the chemical structure-biological functions relationship of CSPGs, both in health state and in genetic disorders, addressing methods represented by genome-wide and crystallographic data as well as molecular modeling and quantitative structure-activity relationship.

Synergism of cortisol and thyrotropin-releasing hormone in lung maturation in fetal sheep

1988 ◽  
Vol 65 (4) ◽  
pp. 1880-1884 ◽  
Author(s):  
G. C. Liggins ◽  
J. C. Schellenberg ◽  
M. Manzai ◽  
J. A. Kitterman ◽  
C. C. Lee
Keyword(s):  
Lung Tissue ◽  
Lavage Fluid ◽  
Thyrotropin Releasing Hormone ◽  
Hormonal Changes ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Releasing Hormone ◽  
Fourfold Increase

The effects of fetal infusions of cortisol and thyrotropin-releasing hormone (TRH) singly and together on pressure-volume relationships and saturated phosphatidylcholine (SPC) concentrations in the lungs were studied in 28 fetal sheep delivered at 128 days of gestation. Four groups each of 7 fetuses were infused with either saline (for 156 h), TRH (25 micrograms/h in 60-s pulses for 156 h), TRH (for 156 h) combined with cortisol (1 mg/h for 84 h), or cortisol (for 84 h). Cortisol had no effect on SPC concentrations, whereas both TRH and cortisol plus TRH increased the concentration of SPC in lavage fluid but not lung tissue. Neither cortisol nor TRH significantly affected lung distensibility [V40; 0.64 +/- 0.04 and 0.57 +/- 0.10 (SE) ml/g, respectively, vs. 0.41 +/- 0.03 ml/g in controls] or stability (V5; 0.24 +/- 0.01 and 0.35 +/- 0.07 ml/g vs. 0.24 +/- 0.03 ml/g), whereas treatment with a combination of the two hormones was associated with a fourfold increase in V40 (1.70 +/- 0.16 ml/g) and V5 (1.03 +/- 0.15 ml/g). Since raised concentrations of cortisol, triiodothyronine, and estradiol-17 beta (treatment with cortisol) had no effect on V40 and V5, whereas similar hormonal changes associated with elevated prolactin levels (treatment with cortisol plus TRH) had marked effects, we conclude that prolactin plays an essential part in the synergism of cortisol and TRH.

scholarly journals Leptin does not influence surfactant synthesis in fetal sheep and mice lungs

2011 ◽  
Vol 300 (3) ◽  
pp. L498-L505 ◽  
Author(s):  
Atsuyasu Sato ◽  
Angelica Schehr ◽  
Machiko Ikegami
Keyword(s):  
Lung Function ◽  
Fetal Lung ◽  
Late Gestation ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Surfactant Synthesis ◽  
Study Protocols ◽  
Fetal Mice ◽  
Pool Sizes

In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122–124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment.

PPARγ activation in late gestation does not promote surfactant maturation in the fetal sheep lung

2021 ◽  
pp. 1-12
Author(s):  
Jiaqi Ren ◽  
Mitchell C. Lock ◽  
Jack R. T. Darby ◽  
Sandra Orgeig ◽  
Stacey L. Holman ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
Alveolar Epithelial Cells ◽  
Late Gestation ◽  
Peroxisome Proliferator ◽  
Phospholipid Synthesis ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Surfactant Synthesis ◽  
Pparγ Agonist

Abstract Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.

Decreases in ovine fetal cartilage sulfate uptake and serum sulfate during gestation

1985 ◽  
Vol 249 (1) ◽  
pp. E115-E120
Author(s):  
F. H. Morriss ◽  
R. N. Marshall ◽  
S. S. Crandell ◽  
B. J. Fitzgerald ◽  
L. Riddle
Keyword(s):  
Human Serum ◽  
Costal Cartilage ◽  
Full Term ◽  
Late Gestation ◽  
In Vitro Assays ◽  
Sulfate Uptake ◽  
Fetal Sheep ◽  
Ovine Fetal ◽  
Serum Sulfate

In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation.

Sign in / Sign up

Export Citation Format

Share Document