Age Differences in the Effect of Hydrocortisone on the Synthesis of Insoluble Elastin in Aortic Tissue of Growing Chicks

Keeley, F. W.; Johnson, Dylan

doi:10.3109/03008208709006980

Cited by 24 publications

(9 citation statements)

References 35 publications

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“…Such information is useful for understanding the potential effects on the perinatal lung mechanics of glucocorticoids, which are widely used in perinatal medicine. Our finding of the stimulatory effects on elastin synthesis is not unique to RPF but has been demonstrated in cell types of diverse animal species (28)(29)(30). However, our finding seems contrary to the finding of Foster et al (31), who, examining the explcnt culture of the 10-d chick embryo lung, did not detect TE stimulation by glucocorticoids (3 1).…”

Section: 3contrasting

confidence: 57%

Developmental Changes of Tropoelastin Synthesis by Rat Pulmonary Fibroblasts and Effects of Dexamethasone

et al. 1990

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ABSTRACT. Lung elastin is an important extracellular structural protein and it has been postulated that it plays a regulatory role in alveolar formation. To study the developmental regulation of elastin gene expression, we examined the tropoelastin (TE) production in primary culture of rat pulmonary fibroblasts (RPF). We found that developmental changes in elastin production as assessed by T E synthesis and 3.6-kb TE mRNA levels were similar for RPF and whole tissue except those results from late gestation animals, with peak elastin expression occurring 7 d postnatally with a decline out to 21 d. At late gestation (20 d), TE mRNA was barely detectable in RPF but clearly detectable TE mRNA in the whole tissue, indicating that there are elastogenic cells other than RPF in the tissue at this age. When TE-producing cells were treated with dexamethasone, there was a dose-dependent stimulation of T E synthesis with the maximum response at lo-' to lo-" M. Interestingly, dexamethasone had no stimulatory effect on cells from late gestation animals. The developmental window of elastin synthesis in this RPF model between late gestation and 21 d postnatal seems to correlate with the reported period of secondary alveolar formation, and thus we speculate that RPF elastogenic activity reflects that of the alveolar wall. (Pediatr Res 28: 379-382, 1990) Abbreviations RPF, rat pulmonary fibroblast TE, tropoelastin SSC, sodium chloride sodium citrate buffer RT, room temperature TCA, trichloroacetic acid Elastin is an important extracellular protein component that forms a resilient fibrous network in the lung. It gives structural compliance to the tissues and may play an important role in the formation of terminal airsacs/alveoli during perinatal stages in various animals, including humans (1-8). This hypothesis is largely based on morphologic observations of elastin deposition in the lung parenchyma and its timely appearance associated with terminal airsac formation.Elastin is a cross-linked mature form of the protein and proform is secreted as TE, a soluble protein of approximately 72 000-75 000 mol wt (9, 10). Regulation of TE synthesis is poorly understood, partly because the regulatory elements of the gene have not been clearly identified. Recent reports indicate that cultured RPF are elastogenic in contrast to lung fibroblasts from larger animals and thus provide a good model for studying lung elastin metabolism (10). However, ontogeny of TE expression in vitro in relation to the original lung tissues has not been described. It is important, therefore, to better characterize the in vitro phenotype so that RPF can be used to investigate the TE gene expression in the lung.In our study, RPF were isolated from rat tissues of various ages and TE expression was examined at the mRNA and protein levels and compared with the steady-state TE mRNA levels of the original tissues to determine if the TE phenotype is maintained in vitro. We also examined whether dexamethasone modulates TE synthesis of the cultured rat lung cell, inasmuch...

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Section: 3contrasting

confidence: 57%

Developmental Changes of Tropoelastin Synthesis by Rat Pulmonary Fibroblasts and Effects of Dexamethasone

et al. 1990

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“…GCs can stimulate ELN synthesis in rabbit lung, 25 in fetal human lung cells, 26 and in chick aortic tissue in an age-dependent manner. 27 This stimulatory effect of GC on ELN synthesis is most probably transcriptional, as glucoco-corticoid response elements have been identified in the human ELN promoter. 28 Additional mechanisms by which maternal GC could program overexpression of offspring vascular ELN include direct epigenetic modification of the ELN gene (methylation/histone acetylation) or indirect enhancement of ELN mRNA translation mediated by GC-induced inhibition of miR-29c, 16 which targets the ELN gene.…”

Section: Discussionmentioning

confidence: 97%

Long-term effects of maternal undernutrition on offspring carotid artery remodeling: role of miR-29c

Khorram

Chuang

Pearce

2015

J Dev Orig Health Dis

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The purpose of this study was to examine the hypothesis that excess maternal glucocorticoids in response to maternal undernutrition programs the expression of extracellular matrix (ECM) components potentially by miR-29c. We measured the expression of mRNA (qRT-PCR) and protein (Western blot) for collagen 3A1, collagen 4A5 and matrix metalloproteinase 2 (MMP2) in offspring carotid arteries from three groups of dams: 50% food-restricted in latter half of gestation [maternal undernutrition (MUN)], MUN dams who received metyrapone (MET) (500 mg/ml ) in drinking water from day 10 of gestation to term, and control dams fed an ad libitum diet. The expression of miR-29c was significantly decreased at 3 weeks, 3 months and 9 months in MUN carotid arteries, and these decreases in expression were partially blocked by treatment of dams with MET. The expression pattern of ECM genes that are targets of miR-29c correlated with miR-29c expression. Expression of mRNA was increased for elastin (ELN) and MMP2 mRNA in 3-week MUN carotids; in 9-month carotids there were also significant increases in expression of Col3A1 and Col4A5. These changes in mRNA expression of ECM genes at 3 weeks and 9 months were blocked by MET treatment. Similarly, the expression of ELN and MMP2 proteins at 3 weeks were increased in MUN carotids, and by 9 months there were also increases in expression of Col3A1 and Col4A5, which were blocked by MET in MUN carotids. Overall, the results demonstrate a close correlation between expression of miR-29c and the ECM proteins that are its targets thus supporting our central hypothesis.

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confidence: 99%

“…Glucocorticoid regulation of elastin synthesis has not been studied in dermis; however, in other tissues, both up-and down-regulation have been observed [15]. Elastin synthesis is stimulated in differentiating connective tissue, such as nuchal ligament, lung, and blood vessels, as well as in cultured cells derived from these tissues [3], whereas in postnatal blood vessels, glucocorticoids down-regulate elastin synthesis [29].To determine the effect of glucocorticoids on elastin synthesis in dermal fibroblasts, and to extend our studies of abnormal glucocorticoid regulation of matrix synthesis in keloid fibroblasts, we examined the rate of elastin accumulation and elastin mPJVA levels in fibroblasts from keloids and from normal adult and fetal dermis, and the effect of hydrocortisone on these indices. …”

mentioning

confidence: 99%

Glucocorticoid Regulation of Elastin Synthesis in Human Fibroblasts: Down-Regulation in Fibroblasts from Normal Dermis But Not From Keloids

Russell

Trupin

Kennedy

et al. 1995

Journal of Investigative Dermatology

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Keloids arise as benign connective tissue masses at sites of injury in genetically predisposed individuals. In addition to excessive collagen accumulation, there is biochemical and histologic evidence of elastic tissue. Previous studies showed that glucocorticoid regulation of collagen synthesis differs in fibroblasts from normal adult dermis and keloids. To define further the abnormal regulation of matrix synthesis in keloid fibroblasts, we examined glucocorticoid regulation of elastin synthesis. The basal level of elastin synthesis was significantly higher in keloid than in normal cells, and hydrocortisone reduced synthesis of elastin and elastin mRNA in normal but not in keloid fibroblasts. We had shown previously that fibroblasts from fetal dermis resembled keloid fibroblasts in glucocorticoid regulation of growth and collagen synthesis. In this study, glucocorticoids failed to down-regulate elastin synthesis in fetal cells that had not differentiated to produce normal levels of elastin, whereas fetal cells with normal elastin production exhibited glucocorticoid down-regulation. Abnormal regulation in keloid cells was independent of cell density and was confined to fibroblasts cultured from the keloid nodule. These findings reinforce the conclusion that a matrix-regulatory pathway is deranged in these focal lesions. Coordinate down-regulation of collagen and elastin by hydrocortisone in normal adult dermal fibroblasts and the failure of hydrocortisone to down-regulate synthesis of either protein in keloid cells support the existence of common elements in the regulatory pathways of these two matrix proteins.

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Age Differences in the Effect of Hydrocortisone on the Synthesis of Insoluble Elastin in Aortic Tissue of Growing Chicks

Cited by 24 publications

References 35 publications

Developmental Changes of Tropoelastin Synthesis by Rat Pulmonary Fibroblasts and Effects of Dexamethasone

Developmental Changes of Tropoelastin Synthesis by Rat Pulmonary Fibroblasts and Effects of Dexamethasone

Long-term effects of maternal undernutrition on offspring carotid artery remodeling: role of miR-29c

Glucocorticoid Regulation of Elastin Synthesis in Human Fibroblasts: Down-Regulation in Fibroblasts from Normal Dermis But Not From Keloids

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