Journal of Investigative Dermatology (1995) 104, 518–522; doi:10.1111/1523-1747.ep12606007
Topical Tretinoin Increases the Tropoelastin and Fibronectin Content of Photoaged Hairless Mouse Skin
Elaine Schwartz1 and Lorraine H Kligman2
- 1Department of Dermatology, Mt. Sinai School of Medicine, New York, New York, U.S.A.
- 2University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
Received 10 August 1994; Revised 17 December 1994; Accepted 27 December 1994.
Top of pageAbstract
Topical tretinoin treatment of photoaged hairless mice has been shown in previous studies to stimulate formation of a subepidermal zone of new connective tissue characterized by enhanced collagen synthesis. The aims of this study were to localize and/or quantify elastin, fibronectin, and glycosaminoglycans in the same model. Hairless mice (Skh-1) were irradiated thrice weekly for 10 weeks with gradually increasing doses of ultraviolet (up to 4.5 minimal erythema doses per exposure) from Westinghouse FS-40 bulbs. Mice were then treated five times a week with either 0.05% tretinoin, the ethanol:propylene glycol vehicle, or nothing for another 10 weeks. Controls included mice sacrificed after 10 weeks of ultraviolet treatment and age-matched untreated animals. The distribution of elastin and fibronectin was examined by immunofluorescence microscopy, which revealed fine fibrils In the subepidermal zone in tretinoin-treated skin. A quantitative slot-blot immunobinding assay showed that tretinoin induced a threefold higher amount of tropoelastin compared with controls. Insoluble elastin content (desmosine levels) was similar in all groups. Although fibronectin content was increased by ultraviolet radiation, tretinoin treatment induced the largest increase. In contrast, the amount of glycosaminoglycans, although increased by UVB radiation, was reduced by tretinoin treatment.
Keywords:
glyconsaminoglycans, elastin, desmosine, UV radiation
Top of pageReferences
- Kligman, LH, Akin, FJ, Kligman, AM: Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens. J Invest Dermatol 1982 78: 181–189, | Article | PubMed | ISI | ChemPort |
- Kligman, LH, Akin, FJ, Kligman, AM: Sunscreens promote repair of ultraviolet radiation-induced dermal damage. J Invest Dermatol 1983 81: 98–101,
- Kligman, LH, Chen, HD, Kligman, AM: Topical retinoic acid enhances the repair of ultraviolet damaged dermal connective tissue. Connect Tissue Res 1984 12: 139–150, | PubMed | ISI | ChemPort |
- Kligman, LH: Effects of all-trans retinoic acid on the dermis of hairless mice. J Am Acad Dermatol 1986 15: 779–785,
- Bryce, GF, Bogdan, NJ, Brown, CC: Retinoic acids promote the repair of the dermal damage and the effacement of wrinkles in the UVB-irradiated hairless mouse. J Invest Dermatol 1988 91: 175–180, | Article | PubMed | ISI | ChemPort |
- Schwartz, E, Cruickshank, FA, Mezick, JA, Kligman, LH: Topical all-trans retinoic acid stimulates collagen synthesis in vivo. J Invest Demtatol 1991 96: 975–978,
- Chen, S, Kiss, I, Tramposch, KM: Effects of all-trans-retinoic acid on UVB-irradiated and non-irradiated hairless mouse skin. J Invest Dermatol 1992 98: 248–254, | Article | PubMed | ISI | ChemPort |
- Kim, HJ, Bogdan, NJ, D'Agostaro, LS, Gold, LI, Bryce, GF: Effect topical retinoic acid on the levels of collagen mRNA during repair of UVB-induced dermal damage in the hairless mouse and the possible role of TGF-
as a mediator. J Invest Dermatol 1992 98: 359–363, - Bissett, DL, Hannon, DP, Orr, TV: An animal model of solar aged skin. Histologic, physical and visible changes in chronically UV-irradiated hairless mouse skin. Photochem Photobiol 1987 46: 367–378, | PubMed | ISI | ChemPort |
- Fourtanier, A, Berrebi, C, Charles, N, Medaisko, C, Noblet, JP: Influence of UV light on natural skin aging in hairless mice. Cosmetic Dermatol 1986 1: 289–300,
- Sams, WM, Smith, JG: The histochemistry of chronically sun damaged skin. J Invest Dermatol 1964 37: 447–452,
- Kligman, AM: Early destructive effects of sunlight on human skin. JAMA 1969 210: 2377–2380, | Article | PubMed | ChemPort |
- Menter, JM, Pearl, WS, Yadven, MW, Willis, I: UV-induced elevation of skin glycosaminoglycan levels. I: Rapid measurement of skin glycosaminoglycans by titration with acridine orange. Photochem Photobiol 1983 38: 481–486,
- Schwartz, E: Connective tissue alterations in the skin of ultraviolet irradiated hairless mice. J Invest Dermatol 1988 91: 158–161, | Article | PubMed | ISI | ChemPort |
- Chen, VL, Fleischmajer, R, Schwartz, E, Palaia, M, Timp1, R: Immunochemistry of elastotic material in sun damaged skin. J Invest Dermatol 1986 87: 334–337, | Article | PubMed | ISI | ChemPort |
- Smith, JG, Davidson, EA, Taylor, RW: Human cutaneous mucopolysaccharides: the effects of age and chronic sun damage. In: Montagna W (ed.). Advances in Biology of Skin. Vol. 6, Aging 1965, pp 211–218,
- Chatterjee, R, Benzinger, MJ, Ritter, JL, Bissett, DL: Chronic ultraviolet B radiation-induced biochemical changes in the skin of hairless mice. Photochem Photobiol 1990 51: 91–97, | PubMed | ISI | ChemPort |
- Chen, S, Beehler, B, Sugimoto, G, Tramposch, KM: Effects of all-trans retinoic acid on glycosaminoglycan synthesis in photodamaged hairless mouse skin. J Invest Dermatol 1993 101: 237–239,
- Kligman, AM, Grove, GL, Hirose, R, Leyden, JJ: Topical tretinoin for photoaged skin. J Am Acad Dermatol 1986 15: 836–839, | PubMed | ISI | ChemPort |
- Ellis, CN, Weiss, JS, Hamilton, TA, Headington, JT, Zelickson, AS, Voorhees, JJ: Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin. J Am Acad Dermatol 1990 23: 629–637,
- Woodley, DT, Zelickson, AJ, Briggaman, RA, Hamilton, TA, Weiss, JA, Ellis, CN, Voorhees, JJ: Treatment of photoaged skin with topical tretinoin increases dermal-epidermal anchoring fibrils. A preliminary report. JAMA 1990 263: 3057–3059, | PubMed |
- Griffiths, CEM, Russman, AN, Majmudar, G, Singer, RS, Hamilton, TA, Voorhees, JJ: Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 1993 329: 530–535, | Article | PubMed | ISI | ChemPort |
- Lunden, A, Berne, B, Michaelsson, G: Topical retinoic acid treatment of photoaged skin: its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid. Acta Derm Venereol (Stockh) 1992 72: 423–427,
- Varani, J, Nickoloff, BJ, Dixit, VM, Mitra, RJ, Voorhees, JJ: All-trans retinoic acid stimulates growth of adult human keratinocytes cultured in growth factor-deficient medium, inhibits production of thrombospondin and fibronectin, and reduces adhesion. J Invest Dermatol 1989 93: 449–454, | Article | PubMed | ISI | ChemPort |
- Varani, J, Mitra, RS, Gibbs, D, Phan, SH, Dixit, VM, Mitra, R Jr, Wang, T, Siebert, KJ, Nickoloff, BJ, Voorhees, JJ: All trans retinoic acid stimulates growth and extracellular matrix production in growth-inhibited cultured human skin fibroblasts. J Invest Dermatol 1990 94: 717–723, | Article | ISI | ChemPort |
- Varani, J, Astrom, A, Griffiths, CEM, Voorhees, JJ: Induction of proliferation of growth inhibited keratinocytes and fibroblasts in monolayer culture by sodium lauryl sulfate: comparison with all-trans retinoic acid. J Invest Dermatol 1991 97: 917–921, | Article | PubMed | ISI | ChemPort |
- Kligman, LH: Luna's technique–a beautiful stain for elastin. Am J Dermatopathol 1981 3: 199–201,
- Jahn, R, Schiebler, W, Greengard, P: A quantitative dot-immunobinding assay for proteins using nitrocellulose membrane filters. Proc Natl Acad Sci USA 1984 81: 1684–1687,
- Schwartz, E, Cruickshank, FA, Lebwohl, M: Determination of desmosines in elastin-related skin disorders by isocratic high performance liquid chromatography. Exp Mol Pathol 1990 52: 63–68,
- Schwartz, E, Mezick, JA, Gendimenico, GJ, Kligman, LH: The in vivo prevention of corticosteroid-induced skin atrophy by tretinoin in the hairless mouse is accompanied by modulation of collagen, glycosaminoglycans, and fibronectin. J Invest Dermtol 1994 102: 241–246,
- Ross, SC, Osborn, TG, Dorner, RW, Zucker, J: Glycosaminoglycan content in the skin of the tight-skin mouse. Arthritis Rheum 1983 26: 653–657,
- Bitter, T, Muir, HM: A modified uronic acid carbazole reaction. Anal Biochem 1962 4: 330–334, | Article | PubMed | ISI | ChemPort |
- Margelin, D, Fourtanier, A, Thevenin, T, Medaisko, C, Breton, M, Picard, J: Alterations of proteoglycans in ultraviolet irradiated skin. Photochem Photobiol 1993 58: 211–218,
- Kligman, LH, Mezick, JA, Capetola, RJ, Thorne, EG: Lifetime topical application of tretinoin to hairless mice. Acta Derm Venereol (Stockh) 1992 72: 418–422,
- Fisher, GJ, Tavakkol, A, Griffiths, CEM, Elder, JT, Zhang, Q-Y, Finkel, L, Danielpour, D, Glick, AB, Highley, H, Ellingsworth, L, Voorhees, JJ: Differential modulation of transforming growth factor-
l expression and mucin deposition by retinoic acid and sodium lauryl sulfate in human skin. J Invest Dermatol 1992 98: 102–108, | Article | PubMed | ISI | ChemPort | - Kligman, LH: The hairless mouse and photoaging: yearly review. Photochem Photobiol 1991 54: 1109–1118,
- Kligman, AM, Graham, GF: Histological changes in facial skin after daily application of tretinoin for 5 to 6 years. J Derm Treatment 1993 4: 113–117,