Decreased elastin synthesis in normal development and in long-term aortic organ and cell cultures is related to rapid and selective destabilization of mRNA for elastin.

We have previously shown that aortic organ cultures from 1- to 3-day-old chickens initially mimic the high levels of elastin production seen in vivo. However, more prolonged incubation of these tissues results in decreased synthesis of elastin. In the present study, we demonstrate that decreased production of elastin in these aortic organ cultures is selective for elastin compared with collagen and is correlated with decreased steady state levels of mRNA for elastin. These decreases in steady state levels of elastin mRNA are due at least in part to a rapid and selective destabilization of mRNA for elastin, the half-life of which falls from approximately 25 hours in fresh aortic tissues to approximately 15 hours after incubation for only 8 hours. Destabilization of elastin mRNA can be prevented by incubation in the presence of blockers of DNA transcription (5,6-dichlorobenzimidazole riboside and actinomycin D) and mRNA translation (cycloheximide). Furthermore, the half-life of aortic elastin mRNA decreases from approximately 25 hours in the 1-day-old chicken to approximately 7 hours in the 8-week-old chicken, demonstrating that destabilization of mRNA is an important contributing factor in the decline in production of aortic elastin taking place during normal postnatal growth.

[1]  C. Berry,et al.  The growth and development of the rat aorta. II. Changes in nucleic acid and scleroprotein content. , 1972, Journal of anatomy.

[2]  R. Ross,et al.  THE ELASTIC FIBER A REVIEW , 1973 .

[3]  D. McCloskey,et al.  Chemical Composition of the Rabbit Aorta during Development , 1974, Circulation research.

[4]  N. Blumenkrantz,et al.  Simple procedures for determination of [14C] hydroxyproline. , 1975, Analytical biochemistry.

[5]  S. H. Jackson,et al.  Proline recycling during collagen metabolism as determined by concurrent 18O2-and 3H-labeling. , 1975, Biochimica et biophysica acta.

[6]  Gerrity Rg,et al.  The aortic tunica media of the developing rat. I. Quantitative stereologic and biochemical analysis. , 1975 .

[7]  F. Keeley.  Detection and estimation of newly synthesized soluble elastin using a hydroxyproline label. , 1977, Advances in experimental medicine and biology.

[8]  S. Rettig,et al.  Crystal and molecular structures of 2,2,4,4,6,8,8-heptamethyl-6-methylamino-1,3,5-triaza-2,4,6,8(PV)-tetraphosphorin and 2,2,4,4,6,8,8-heptamethyl-6-methylamino-7-benzoyl-1,3,5-triaza-2,4,6,8(PV)-tetraphosphorin , 1978 .

[9]  Keeley Fw.  The synthesis of soluble and insoluble elastin in chicken aorta as a function of development and age. Effect of a high cholesterol diet. , 1979 .

[10]  M. Lefevre,et al.  Aorta elastin turnover in normal and hypercholesterolemic Japanese quail. , 1980, Biochimica et biophysica acta.

[11]  J. Rosenbloom,et al.  Correlation of functional elastin messenger ribonucleic acid levels and rate of elastin synthesis in the developing chick aorta. , 1980, Biochemistry.

[12]  F. Keeley,et al.  Measurement of the absolute synthesis of soluble and insoluble elastin by chick aortic tissue. , 1983, Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire.

[13]  R. Paul.  Functional compartmentalization of oxidative and glycolytic metabolism in vascular smooth muscle. , 1983, The American journal of physiology.

[14]  J. L. Alford,et al.  Developmental changes in collagen and elastin biosynthesis in the porcine aorta. , 1986, Developmental biology.

[15]  H. Moses,et al.  Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. , 1987, The Journal of clinical investigation.

[16]  C. Franzblau,et al.  Elastin mRNA levels and insoluble elastin accumulation in neonatal rat smooth muscle cell cultures. , 1988, Biochemistry.

[17]  M. Miller,et al.  Synthesis of soluble and insoluble elastins in cultures of chick aortic cells. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[18]  P. Bornstein,et al.  Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Lukas C. Kühn,et al.  A stem-loop in the 3′ untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm , 1988, Cell.

[20]  J. Davidson,et al.  The elastogenic effect of recombinant transforming growth factor-beta on porcine aortic smooth muscle cells. , 1988, Biochemical and biophysical research communications.

[21]  J. Foster,et al.  Evidence for insulin-like growth factor-I regulation of chick aortic elastogenesis. , 1989, Matrix.

[22]  J. A. Chapman,et al.  Pleomorphism in type I collagen fibrils produced by persistence of the procollagen N-propeptide. , 1989, Journal of molecular biology.

[23]  D. Badesch,et al.  Insulin-like growth factoristimulates elastin synthesis by bovine pulmonary arterial smooth muscle cells , 1989 .

[24]  F. Keeley,et al.  Factors affecting the production of insoluble elastin in aortic organ cultures. , 1990, Connective tissue research.

[25]  F. Keeley,et al.  Pattern of accumulation of elastin and the level of mRNA for elastin in aortic tissue of growing chickens. , 1990, Archives of biochemistry and biophysics.

[26]  E. Hay,et al.  Cell Biology of Extracellular Matrix , 1988, Springer US.

[27]  R. Mecham,et al.  Inhibition of tropoelastin expression by 1,25-dihydroxyvitamin D3. , 1991, Connective tissue research.

[28]  R. Mecham,et al.  Hypoxia-induced inhibition of tropoelastin synthesis by neonatal calf pulmonary artery smooth muscle cells. , 1991, American journal of respiratory cell and molecular biology.

[29]  R. Pierce,et al.  Phorbol ester-mediated downregulation of tropoelastin expression is controlled by a posttranscriptional mechanism. , 1992, Biochemistry.

[30]  S. McGowan.  Influences of endogenous and exogenous TGF-beta on elastin in rat lung fibroblasts and aortic smooth muscle cells. , 1992, The American journal of physiology.

[31]  J. Uitto,et al.  Transforming growth factor-beta up-regulates elastin gene expression in human skin fibroblasts. Evidence for post-transcriptional modulation. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[32]  J. Rosenbloom,et al.  Insulin-like growth factor-I regulates transcription of the elastin gene. , 1993, The Journal of biological chemistry.

[33]  P. Robson,et al.  Characterization of lamprin, an unusual matrix protein from lamprey cartilage. Implications for evolution, structure, and assembly of elastin and other fibrillar proteins. , 1993, The Journal of biological chemistry.

[34]  J. Rosenbloom,et al.  Extracellular matrix 4: The elastic fiber , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  J. Rosenbloom,et al.  Developmental regulation of aortic elastin gene expression involves disruption of an IGF-I sensitive repressor complex. , 1993, Biochemical and biophysical research communications.

[36]  D. Volpin,et al.  Regulation of the human elastin promoter in chick embryo cells. Tissue-specific effect of TGF-beta. , 1993, Biochimica et biophysica acta.

[37]  A. Sachs,et al.  Messenger RNA degradation in eukaryotes , 1993, Cell.

[38]  F. Keeley,et al.  Relative efficiency of incorporation of newly synthesized elastin and collagen into aorta, pulmonary artery and pulmonary vein of growing pigs. , 1993, Connective tissue research.

[39]  Z. Dominski,et al.  Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3'-untranslated region of rat tyrosine hydroxylase mRNA. , 1994, The Journal of biological chemistry.

[40]  M. Goldberg,et al.  Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. , 1994, The Journal of biological chemistry.

[41]  D. Volpin,et al.  Identification of a TGF-β Responsive Element in the Human Elastin Promoter , 1994 .

[42]  W. Taylor,et al.  Comparison of glyceraldehyde-3-phosphate dehydrogenase and 28S-ribosomal RNA gene expression as RNA loading controls for northern blot analysis of cell lines of varying malignant potential. , 1994, Analytical biochemistry.

[43]  J. Rosenbloom,et al.  Tissue-specific and developmentally regulated expression of human elastin promoter activity in transgenic mice. , 1994, The Journal of biological chemistry.