Modulation of tropoelastin production and elastin messenger ribonucleic acid activity in developing sheep lung

Shibahara, Shigeki; Davidson, Jeffrey M.; Smith, Kitty P.; Crystal, Ronald G.

doi:10.1021/bi00526a009

Cited by 60 publications

(31 citation statements)

References 24 publications

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“…With respect to lung, the observations to date (11,33,42) suggest that chick aorta and lung tropoelastin are nearly identical in size and have similar chemical properties and composition (Table 1). There also appear to be close similarities between sheep nuchal ligament and sheep lung elastin (15,41).…”

Section: Components Of Elastic Fiber: Isolation and Composition Of Elmentioning

confidence: 75%

“…Later investigations, however, were unable to confirm the presence of soluble proelastin greater than 76,000-78,000 daltons (11,15,16,41,(46)(47)(48)(49). When translation systems are used utilizing messenger RNA preparations from aortae and lung, the major elastinlike products of translation appear to resemble tropoelastin with perhaps a short extension peptide (2,15,16,41,42,48,49 (34,35). Protocol IV, based on cyanogen bromide cleavage, is useful when it is certain that the elastin to be isolated contains no methionyl residues (5,32).…”

Section: Components Of Elastic Fiber: Isolation and Composition Of Elmentioning

confidence: 94%

“…Tropoelastin appears to be secreted from cells in the form of a 72,000 molecular weight protein (5,10,11,15,41). This protein has now been isolated from the aorta and ligamentum of various species (1,5,10), and chick lung (33,42).…”

Section: Components Of Elastic Fiber: Isolation and Composition Of Elmentioning

confidence: 99%

“…Typical data for the relative distribution of crosslinking amino acids in calf lung elastin is given in Table (C H2) (41,(71)(72)(73)(74), but has yet to be well characterized from a lung tissue source. Lysyl oxidase activity is inhibited or reduced upon administration of lathyrogens (73,75).…”

Section: Post-translational Steps In Elastic Fiber Formationmentioning

confidence: 99%

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Elastin metabolism and chemistry: potential roles in lung development and structure.

Rucker¹,

Dubick²

1984

Environ Health Perspect

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Elastic fibers are important for elasticity and extensibility of lung tissue. In the developing lung, elastic fibers appear in greatest numbers during the process or period of alveolarization. A variety of mesenchymal cells in lung appear responsible for elastin synthesis. Elastin is a novel protein both from the standpoint of its processing into elastic fibers and chemical properties. For example, elastin undergoes posttranslational modification before its assembly into fibers. These steps include limited proteolysis, hydroxylation of prolyl residues and the oxidative deamination of lysyl residues prior to their incorporation into the crosslinks that covalently bond together polypeptide chains of elastin. The crosslinking amino acids include lysinonorleucine, merodesmosine and desmosine isomers. A key enzyme that controls this process is lysyl oxidase. Lysyl oxidase is a copper metalloprotein whose activity is responsive to and modulated by environmental insults, nutrition deficiencies and the administration of various pharmacological agents. Regarding chemical properties, elastin is one of the most apolar proteins secreted by mammalian cells. Moreover, elastin is one of the most long-lived proteins secreted into the extracellular matrix. In relationship to its processing into elastic fibers and chemical properties, details related to major aspects of elastin metabolism as well as speculation on its potential as a factor in lung development and disease are discussed.

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Section: Components Of Elastic Fiber: Isolation and Composition Of Elmentioning

confidence: 75%

Section: Components Of Elastic Fiber: Isolation and Composition Of Elmentioning

confidence: 94%

Section: Components Of Elastic Fiber: Isolation and Composition Of Elmentioning

confidence: 99%

Section: Post-translational Steps In Elastic Fiber Formationmentioning

confidence: 99%

See 2 more Smart Citations

Elastin metabolism and chemistry: potential roles in lung development and structure.

Rucker¹,

Dubick²

1984

Environ Health Perspect

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“…The increase in TE synthesis by RPF was dose-response curve was similar to the mRNA changes, with the a specific, developmentally regulated event that cannot be totally maximum at lo-' to M with no differences between 7-d related to the overall increase in the protein synthesis because the magnitude of increase in TE production was greater than that for total protein. Signals for rapid decline of TE synthesis postnatally are unclear but developmental windows of the synthetic period have been described in various elastogenic cells/ tissues examined (18)(19)(20)(21)(22). Shibahara et al (22) have shown that in fetal sheep lung tissue, the period of rapid TE synthesis starts in the latter half of gestation, which is similar to bovine lung tissue (23) but distinct from rat lung, where elastin accumulation occurs mainly in the first 2 postnatal wk and becomes quiescent by 3 wk (1 1).…”

Section: 3mentioning

confidence: 99%

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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Elastogenesis in the developing chick lung is transcriptionally regulated

et al. 1998

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The overall goals of this study were to establish the level at which elastin gene expression is regulated during chick lung embryogenesis and to identify the temporal and spatial relationships among elastogenesis, smooth muscle cell differentiation, and cell proliferation. A comparison of lung elastin mRNA and transcriptional levels during embryogenesis shows that elastin expression is developmentally regulated at the transcriptional level. The increase in elastogenic activity occurs during the late stages of lung embryogenesis and coincides with terminal maturation of the tertiary bronchi. In situ hybridization analysis demonstrates that the increase in elastin mRNA expression is confined to the tertiary bronchial respiratory subunits, connective tissue septa, and supporting vasculature of the lung parenchyma. Immunohistochemical localization of smooth muscle cell α‐actin and tropoelastin suggests that α‐actin–immunoreactive cells of the lung parenchyma are a major contributor to the increase in elastin expression during embryogenesis. This observation is also reflected by Northern blot analysis, which demonstrates a temporal coincidence in the increase of both α‐actin and elastin mRNA levels. Histone mRNA expression, which was used as an index of cellular proliferation, reveals a level and spatial pattern inversely related to that of the elastin transcript. Tissue transfections of chick lungs isolated from 18‐day embryos with various elastin gene deletion/reporter constructs illustrate that the elastin promoter is not promiscuous within a tissue environment and that sequences spanning the −500 to +2 region are capable of directing promoter activity spatially comparable to the endogenous elastin gene. Dev. Dyn. 1998;213:170–181. © 1998 Wiley‐Liss, Inc.

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Modulation of tropoelastin production and elastin messenger ribonucleic acid activity in developing sheep lung

Cited by 60 publications

References 24 publications

Elastin metabolism and chemistry: potential roles in lung development and structure.

Elastin metabolism and chemistry: potential roles in lung development and structure.

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

Elastogenesis in the developing chick lung is transcriptionally regulated

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