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Gene Review

Eln  -  elastin

Mus musculus

Synonyms: AI385707, AI480567, E030024M20Rik, Elastin, Tropoelastin, ...
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Disease relevance of Eln

  • Levels of tropoelastin mRNA and protein were lower in aortas and isolated SMCs of adult transgenic mice expressing the human B-myb gene, driven by the basal cytomegalovirus promoter, compared with age-matched wild type (WT) animals [1].
  • The pathogenesis of aneurysm formation was studied in Blotchy (Blo) mice which have a hereditary defect in collagen and elastin cross-linking [2].
  • The most upregulated gene in the smoke group, MMP12, is a matrix metalloproteinase that preferentially degrades elastin and has been implicated in COPD development [3].
  • Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion [4].
  • However, lack of elastin is not associated with endothelial damage, thrombosis or inflammation, which occur in models of atherosclerosis [5].

High impact information on Eln

  • Thus elastin polymer deposition is a crucial aspect of elastic fiber maintenance and is dependent on LOXL1, which serves both as a cross-linking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin [6].
  • Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)--a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema [7].
  • Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood [8].
  • Disruption of elastin is enough to induce subendothelial proliferation of smooth muscle and may contribute to obstructive arterial disease [5].
  • Disruption of elastin was believed to lead to dissection of arteries, but we showed that mutations in one allele encoding elastin cause a human disease in which arteries are blocked, namely, supravalvular aortic stenosis [5].

Chemical compound and disease context of Eln


Biological context of Eln


Anatomical context of Eln

  • Tropoelastin mRNA expression in aortas of 6-day-old neonatal transgenic and WT animals was comparable [1].
  • The level of elastin mRNA transcripts was also markedly lower in both cell lines in comparison to controls [17].
  • We report that fibulin-5 protein potently induces elastic fiber assembly and maturation by organizing tropoelastin and cross-linking enzymes onto microfibrils [18].
  • Our results indicate that fibulin-5 is coordinately expressed and regulated with elastin in lung fibroblasts and may serve a key role during lung injury and repair [19].
  • The chemotactic response was significantly diminished by pretreatment of macrophages with lactose or with the elastin-derived peptide VGVAPG and by pretreatment of samples with a monoclonal antibody directed against an EBP recognition sequence [20].

Associations of Eln with chemical compounds

  • Collectively, these data support a model whereby the elastin gene product, signaling through the VGVAPG domain, directly induces VSMC myofibrillogenesis [21].
  • Previous studies have established that cross-links in collagen and elastin are decreased in these animals due to impaired formation of lysine-derived aldehydes [22].
  • A quantitative slot-blot immunobinding assay showed that tretinoin induced a threefold higher amount of tropoelastin compared with controls [23].
  • Lysyl oxidase activity in biological samples is traditionally and most reliably assessed by tritium release end-point assays using radiolabeled collagen or elastin substrates involving laborious vacuum distillation of the released tritiated water [24].
  • There was a 147% increase in insoluble elastin with propranolol and a lesser increase of 54% in insoluble collagen [25].

Enzymatic interactions of Eln


Co-localisations of Eln


Regulatory relationships of Eln

  • Expression of an autoactivating form of MMP-9 in macrophages in vitro greatly enhances elastin degradation and induces significant plaque disruption when overexpressed by macrophages in advanced atherosclerotic lesions of apoE-/- mice in vivo [28].
  • Our studies show that fibulin-1 is expressed surrounding the primordial VSMCs of the vessel wall before elastin precursors are present and suggest that differential expression of the JB3 antigen (Wunsch et al., 1994) may be indicative of early diversity among embryonic VSMCs [29].
  • Pharmacological modulation of the antioxidant enzymes activities and the concentration of peroxidation products in fibroblasts stimulated with elastin peptides [30].

Other interactions of Eln

  • The linkage and genetic distances between Eln and the closest molecular markers used in this study are centromere-D5Mit95, D5Mit96-6.7 cM-Gus, Eln-4.0 cM-Zp3-telomere [31].
  • The authors systematically analysed the expression of elastin; collagen types I, III, IV; laminin; and fibronectin during mouse detrusor muscle development, a period during which downregulation of detrusor proliferation and increasing smooth muscle differentiation is known to occur [32].
  • CONCLUSIONS: Our findings demonstrate that aortic extracts from mgR/mgR mice can stimulate macrophage chemotaxis by interaction with EBP and show that a fibrillin-1 fragment possesses chemotactic stimulatory activity similar to that of elastin degradation peptides [20].
  • Specifically, levels of elastin and glycosoaminoglycans are increased, collagen fibers are more compactly organized, and matrix modulators like integrins, TGFbeta1, and matrix metalloproteinases (MMPs) are altered both basally and after wounding in Smad3 knockout mice [33].
  • We studied the expression of LTBP-2 in the developing mouse and rat by in situ hybridization, using tropoelastin expression as a marker of tissues participating in elastic fiber formation [27].

Analytical, diagnostic and therapeutic context of Eln


  1. B-Myb represses elastin gene expression in aortic smooth muscle cells. Hofmann, C.S., Wang, X., Sullivan, C.P., Toselli, P., Stone, P.J., McLean, S.E., Mecham, R.P., Schreiber, B.M., Sonenshein, G.E. J. Biol. Chem. (2005) [Pubmed]
  2. Spontaneous aortic aneurysms in blotchy mice. Andrews, E.J., White, W.J., Bullock, L.P. Am. J. Pathol. (1975) [Pubmed]
  3. Gene expression profiling in lung tissues from mice exposed to cigarette smoke, lipopolysaccharide, or smoke plus lipopolysaccharide by inhalation. Meng, Q.R., Gideon, K.M., Harbo, S.J., Renne, R.A., Lee, M.K., Brys, A.M., Jones, R. Inhalation toxicology. (2006) [Pubmed]
  4. Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. Faury, G., Pezet, M., Knutsen, R.H., Boyle, W.A., Heximer, S.P., McLean, S.E., Minkes, R.K., Blumer, K.J., Kovacs, A., Kelly, D.P., Li, D.Y., Starcher, B., Mecham, R.P. J. Clin. Invest. (2003) [Pubmed]
  5. Elastin is an essential determinant of arterial morphogenesis. Li, D.Y., Brooke, B., Davis, E.C., Mecham, R.P., Sorensen, L.K., Boak, B.B., Eichwald, E., Keating, M.T. Nature (1998) [Pubmed]
  6. Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Liu, X., Zhao, Y., Gao, J., Pawlyk, B., Starcher, B., Spencer, J.A., Yanagisawa, H., Zuo, J., Li, T. Nat. Genet. (2004) [Pubmed]
  7. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Morris, D.G., Huang, X., Kaminski, N., Wang, Y., Shapiro, S.D., Dolganov, G., Glick, A., Sheppard, D. Nature (2003) [Pubmed]
  8. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nakamura, T., Lozano, P.R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C.F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross Jr, J., Honjo, T., Chien, K.R. Nature (2002) [Pubmed]
  9. Laminin regulates a tumor cell chemotaxis receptor through the laminin-binding integrin subunit alpha 6. Blood, C.H., Zetter, B.R. Cancer Res. (1993) [Pubmed]
  10. Differential expression of elastin and alpha 1(I) collagen mRNA in mice with bleomycin-induced pulmonary fibrosis. Lucey, E.C., Ngo, H.Q., Agarwal, A., Smith, B.D., Snider, G.L., Goldstein, R.H. Lab. Invest. (1996) [Pubmed]
  11. Elastin gene expression is upregulated during pulmonary fibrosis. Hoff, C.R., Perkins, D.R., Davidson, J.M. Connect. Tissue Res. (1999) [Pubmed]
  12. Lysosomal cysteine proteases in atherosclerosis. Liu, J., Sukhova, G.K., Sun, J.S., Xu, W.H., Libby, P., Shi, G.P. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  13. Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Drewes, P.G., Yanagisawa, H., Starcher, B., Hornstra, I., Csiszar, K., Marinis, S.I., Keller, P., Word, R.A. Am. J. Pathol. (2007) [Pubmed]
  14. The tissue distribution of murine Abcc6 (Mrp6) during embryogenesis indicates that the presence of Abcc6 in elastic tissues is not required for elastic fiber assembly. Beck, K., Dang, K., Boyd, C.D. J. Mol. Histol. (2005) [Pubmed]
  15. Normal wound healing in mice deficient for fibulin-5, an elastin binding protein essential for dermal elastic fiber assembly. Zheng, Q., Choi, J., Rouleau, L., Leask, R.L., Richardson, J.A., Davis, E.C., Yanagisawa, H. J. Invest. Dermatol. (2006) [Pubmed]
  16. Mapping of Col3a1 and Col6a3 to proximal murine chromosome 1 identifies conserved linkage of structural protein genes between murine chromosome 1 and human chromosome 2q. Schurr, E., Skamene, E., Morgan, K., Chu, M.L., Gros, P. Genomics (1990) [Pubmed]
  17. Expression and accumulation of lysyl oxidase, elastin, and type I procollagen in human Menkes and mottled mouse fibroblasts. Gacheru, S., McGee, C., Uriu-Hare, J.Y., Kosonen, T., Packman, S., Tinker, D., Krawetz, S.A., Reiser, K., Keen, C.L., Rucker, R.B. Arch. Biochem. Biophys. (1993) [Pubmed]
  18. Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. Hirai, M., Ohbayashi, T., Horiguchi, M., Okawa, K., Hagiwara, A., Chien, K.R., Kita, T., Nakamura, T. J. Cell Biol. (2007) [Pubmed]
  19. Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair. Kuang, P.P., Goldstein, R.H., Liu, Y., Rishikof, D.C., Jean, J.C., Joyce-Brady, M. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  20. Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse model and a GxxPG-containing fibrillin-1 fragment. Guo, G., Booms, P., Halushka, M., Dietz, H.C., Ney, A., Stricker, S., Hecht, J., Mundlos, S., Robinson, P.N. Circulation (2006) [Pubmed]
  21. Elastin induces myofibrillogenesis via a specific domain, VGVAPG. Karnik, S.K., Wythe, J.D., Sorensen, L., Brooke, B.S., Urness, L.D., Li, D.Y. Matrix Biol. (2003) [Pubmed]
  22. Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. Rowe, D.W., McGoodwin, E.B., Martin, G.R., Grahn, D. J. Biol. Chem. (1977) [Pubmed]
  23. Topical tretinoin increases the tropoelastin and fibronectin content of photoaged hairless mouse skin. Schwartz, E., Kligman, L.H. J. Invest. Dermatol. (1995) [Pubmed]
  24. A fluorometric assay for detection of lysyl oxidase enzyme activity in biological samples. Palamakumbura, A.H., Trackman, P.C. Anal. Biochem. (2002) [Pubmed]
  25. Propranolol stimulates the crosslinking of matrix components in skin from the aneurysm-prone blotchy mouse. Brophy, C.M., Tilson, J.E., Tilson, M.D. J. Surg. Res. (1989) [Pubmed]
  26. Autocrine growth factor regulation of lysyl oxidase expression in transformed fibroblasts. Palamakumbura, A.H., Sommer, P., Trackman, P.C. J. Biol. Chem. (2003) [Pubmed]
  27. Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development. Shipley, J.M., Mecham, R.P., Maus, E., Bonadio, J., Rosenbloom, J., McCarthy, R.T., Baumann, M.L., Frankfater, C., Segade, F., Shapiro, S.D. Mol. Cell. Biol. (2000) [Pubmed]
  28. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. Gough, P.J., Gomez, I.G., Wille, P.T., Raines, E.W. J. Clin. Invest. (2006) [Pubmed]
  29. Development of the aortic vessel wall as defined by vascular smooth muscle and extracellular matrix markers. Hungerford, J.E., Owens, G.K., Argraves, W.S., Little, C.D. Dev. Biol. (1996) [Pubmed]
  30. Pharmacological modulation of the antioxidant enzymes activities and the concentration of peroxidation products in fibroblasts stimulated with elastin peptides. Gmiński, J., Weglarz, L., Drózdz, M., Goss, M. Gen. Pharmacol. (1991) [Pubmed]
  31. Use of an intron polymorphism to localize the tropoelastin gene to mouse chromosome 5 in a region of linkage conservation with human chromosome 7. Wydner, K.S., Sechler, J.L., Boyd, C.D., Passmore, H.C. Genomics (1994) [Pubmed]
  32. Extracellular matrix protein expression during mouse detrusor development. Smeulders, N., Woolf, A.S., Wilcox, D.T. J. Pediatr. Surg. (2003) [Pubmed]
  33. Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure. Arany, P.R., Flanders, K.C., Kobayashi, T., Kuo, C.K., Stuelten, C., Desai, K.V., Tuan, R., Rennard, S.I., Roberts, A.B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  34. The Pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. Thomassin, L., Werneck, C.C., Broekelmann, T.J., Gleyzal, C., Hornstra, I.K., Mecham, R.P., Sommer, P. J. Biol. Chem. (2005) [Pubmed]
  35. Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. McLaughlin, P.J., Chen, Q., Horiguchi, M., Starcher, B.C., Stanton, J.B., Broekelmann, T.J., Marmorstein, A.D., McKay, B., Mecham, R., Nakamura, T., Marmorstein, L.Y. Mol. Cell. Biol. (2006) [Pubmed]
  36. Reduced transplant arteriosclerosis in plasminogen-deficient mice. Moons, L., Shi, C., Ploplis, V., Plow, E., Haber, E., Collen, D., Carmeliet, P. J. Clin. Invest. (1998) [Pubmed]
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