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Peeling agents and irritants, unlike tretinoin, do not stimulate collagen synthesis in the photoaged hairless mouse

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Abstract

Tretinoin has been shown to stimulate the synthesis of collagen in photoaged human and hairless mouse skin. It has been suggested that this partial reversal of photodamage by tretinoin is a consequence of low-grade inflammation. The purpose of this study was to compare the effect of tretinoin with a number of irritants and peeling agents on collagen synthesis. Hairless mice were irradiated thrice weekly for 10 weeks with UVB. In the 10-week postirradiation period, the mice were treated topically five times per week with tretinoin (0.05%), glycolic acid (10%), benzalkonium chloride (1.0%), sodium lauryl sulfate (5%), croton oil (5%) and the water—propylene glycol vehicle. Microscopic measurements showed that the tretinoin-induced zone of new collagen was twice the depth of that induced by irritants or vehicle. The salt-soluble collagen content was determined by HPLC analysis of hydroxyproline levels. Type III procollagen was quantified by radioimmunoassay. Tretinoin-treated skin had increased amounts of collagen and type III procollagen whereas irritant- and peeling agent-treated skins were similar to vehicle-treated controls. Immunofluorescence studies were confirmatory. These results demonstrate that these agents, unlike tretinoin, do not have the capacity to enhance collagen synthesis. Therefore, it is likely that the effect of tretinoin does not depend upon irritation.

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References

  1. Schwartz E, Cruickshank FA, Mezick JA, Kligman LH (1991) Topical all-trans retinoic acid stimulates collagen synthesis in vivo. J Invest Dermatol 96: 975–978

    Article  PubMed  CAS  Google Scholar 

  2. Kim HJ, Bogdan NJ, D’Agostaro LJ, Gold LI, Bryce GF (1992) Effect of topical retinoic acids on the levels of collagen mRNA during the repair of UVB-induced dermal damage in the hairless mouse and the possible role of TGF-β as a mediator. J Invest Dermatol 98: 359–363

    Article  PubMed  CAS  Google Scholar 

  3. Chen S, Kiss I, Tramposch KM (1992) Effect of all-trans retinoic acid on UVB-irradiated and non-irradiated hairless mouse skin. J Invest Dermatol 98: 248–254

    Article  PubMed  CAS  Google Scholar 

  4. Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). New Engl J Med 329: 530–535

    Article  PubMed  CAS  Google Scholar 

  5. Woodley DT, Zelickson AS, Briggaman RA, Hamilton TA, Weiss JS, Ellis CN, Voorhees JJ (1990) Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils. A preliminary report. JAMA 263: 3057–3059

    Article  PubMed  CAS  Google Scholar 

  6. Kligman AM, Graham GF (1993) Histologic changes in facial skin after daily application of tretinoin for 5 to 6 years. J Dermatol Treat 4: 113–117

    Google Scholar 

  7. Kligman AM, Grove GL, Hirose R, Leyden JJ (1986) Topical tretinoin for photoaged skin. J Am Acad Dermatol 15: 836–859, 886–887

    Article  PubMed  CAS  Google Scholar 

  8. Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ (1988) Treatment of photodamaged facial skin with topical tretinoin. JAMA 259: 527–532

    Article  PubMed  CAS  Google Scholar 

  9. Kligman AM, Thorne EG (1991) Topical therapy of actinic keratoses with tretinoin. In: Marks R (ed) Retinoids in cutaneous malignancy. Blackwell Scientific Publications. Oxford, pp 66–73

    Google Scholar 

  10. Kotrajaras R, Kligman AM (1993) The effect of topical tretinoin on photodamaged facial skin: the Thai experience. Br J Dermatol 129: 302–309

    Article  PubMed  CAS  Google Scholar 

  11. Bhawan J, Palko MJ, Lee J, Labadie RR, Perry BH, Lufrano L, Thorne EG, Gilchrest BS (1995) Reversible histologic effects of tretinoin on photodamaged skin. J Geriatr Dermatol 3: 62–67

    Google Scholar 

  12. Fisher GJ, Esmann J, Griffiths CEM, Talwar HS, Duell EA, Hammerberg C, Elder JT, Karabin GD, Nickoloff BJ, Cooper KD, Voorhees JJ (1991) Cellular, immunologic and biochemical characterization of topical retinoic-acid-treated human skin. J Invest Dermatol 96: 699–707

    Article  PubMed  CAS  Google Scholar 

  13. Varani J, Astrom A, Griffiths CEM, Voorhees JJ (1991) 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 97: 917–921

    Article  PubMed  CAS  Google Scholar 

  14. Marks R, Hill S, Barton SP (1990) The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin. Br J Dermatol 123: 457–466

    Article  PubMed  CAS  Google Scholar 

  15. Danhof IE (1993) Potential reversal of chronological and photoaging of the skin by topical application of natural substances. Phytother Res 7: 553–556

    Google Scholar 

  16. Van Scott EJ, Yu RJ (1984) Hyperkeratinization, corneocyte cohesion and alpha hydroxy acids. J Am Acad Dermatol 11: 867–869

    PubMed  Google Scholar 

  17. Ridge JM, Siegle RJ, Zuckerman J (1990) Use of α-hydroxy acids in the therapy for photoaged skin. J Am Acad Dermatol 23: 932

    PubMed  CAS  Google Scholar 

  18. Van Scott EJ, Yu RJ (1995) Actions of alpha hydroxy acids on skin compartments. J Geriatr Dermatol [Suppl A] 3: 19A-25A

    Google Scholar 

  19. Leyden JJ, Lavker RM, Grove G, Kaidbey KH (1995) Alpha hydroxy acids are more than moisturizers. J Geriatr Dermatol [Suppl A] 3: 33A-37A

    Google Scholar 

  20. Kligman LH (1981) Luna’s technique. A beautiful stain for elastin. Am J Dermatopathol 3: 199–200

    Article  PubMed  CAS  Google Scholar 

  21. Kligman LH, Chen HD, Kligman AM (1984) Topical retinoic acid enhances the repair of ultraviolet damaged dermal connective tissue. Connect Tissue Res 12: 139–150

    PubMed  CAS  Google Scholar 

  22. Schwartz E, Cruickshank FA, Perlish JS, Fleischmajer R (1989) Alterations in dermal collagen in ultraviolet irradiated hairless mice. J Invest Dermatol 93: 142–146

    Article  PubMed  CAS  Google Scholar 

  23. Risteli J, Niemi S, Trivedi P, Maentausta O, Mowat AP, Risteli A (1988) Rapid equilibrium radioimmunoassay for the aminoterminal propeptide of human type III procollagen. Clin Chem 34: 715–718

    PubMed  CAS  Google Scholar 

  24. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72: 248–254

    Article  PubMed  CAS  Google Scholar 

  25. Einarsson S, Josefsson B, Lagerkuist S (1983) Determination of amino acids with 9-fluorenyl-methyl chloroformate and reversed-phase high performance liquid chromatography. J Chromatogr 282: 609–618

    Article  CAS  Google Scholar 

  26. Griffiths CEM, Finkel LJ, Tranfaglia MG, Hamilton TA, Voorhees JJ (1993) An in vivo experimental model for effects of topical retinoic acid in human skin. Br J Dermatol 129: 389–394

    Article  PubMed  CAS  Google Scholar 

  27. Bhawan J, Gonzalez-Serva A, Nehal K, Labadie R, Lufrano L, Thorne EG, Gilchrest BA (1991) Effects of tretinoin on photodamaged skin. Arch Dermatol 127: 666–672

    Article  PubMed  CAS  Google Scholar 

  28. Lesnik RH, Mezick JA, Capetola R, Kligman LH (1989) Topical all-trans-retinoic acid prevents corticosteroid induced skin atrophy without abrogating the antiinflammatory effect. J Am Acad Dermatol 21: 186–190

    Article  PubMed  CAS  Google Scholar 

  29. Schwartz E, Mezick JA, Gendimenico GJ, Kligman LH (1994) In vivo prevention of corticosteroid-induced atrophy by tretinoin in the hairless mouse is accompanied by modulation of collagen, glycosaminoglycans and fibronectin. J Invest Dermatol 102: 241–246

    Article  PubMed  CAS  Google Scholar 

  30. Bécherel P-A, Mossalayi MD, Le Goff L, Debre P, Frances C, Chosidow O, Arock M (1994) Retinoids exert anti-inflammatory effects on human keratinocytes through inhibition of NO and TNF-α secretion (abstract). J Invest Dermatol 103: 422

    Google Scholar 

  31. Wozel G, Chang A, Zultak M, Czarnetzki BM, Happle R, Barth J, Kerkhof PCM van de (1991) The effect of topical retinoids on the leukotriene-B4 induced migration of polymorphonuclear leukocytes into human skin. Arch Dermatol Res 283: 158–161

    Article  PubMed  CAS  Google Scholar 

  32. Clark SD, Kobayashi DK, Welgus HG (1987) Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts. J Clin Invest 80: 1280–1288

    PubMed  CAS  Google Scholar 

  33. Wright JK, Clark IM, Cawston TE, Hazleman BL (1991) The secretion of the tissue inhibitor of metalloproteinases (TIMP) by human synovial fibroblasts is modulated by all-trans retinoic acid. Biochem Biophys Acta 1133: 25–30

    Article  PubMed  CAS  Google Scholar 

  34. Schwartz E, Kligman LH (1995) Topical tretinoin increases the tropoelastin and fibronectin content of photoaged hairless mouse skin. J Invest Dermatol 104: 518–522

    Article  PubMed  CAS  Google Scholar 

  35. Kligman LH, Mezick JA, Capetola RJ, Thorne EG (1992) Lifetime topical application of tretinoin to hairless mice. Acta Derm Venereol (Stockh) 72: 418–422

    CAS  Google Scholar 

  36. Fisher GJ, Tavakkol A, Griffiths CEM, Elder JT, Zhang Q-Y, Finkel L, Danielpour D, Glick AB, Highley H, Ellingsworth L, Voorhees JJ (1992) Differential modulation of transforming growth factor-B1 expression and mucin deposition by retinoic acid and sodium lauryl sulfate in human skin. J Invest Dermatol 98: 102–108

    Article  PubMed  CAS  Google Scholar 

  37. Van Scott EJ, Yu RJ (1989) Alpha hydroxy acids: therapeutic potentials. Can J Dermatol 1: 108–112

    Google Scholar 

  38. Lavker RM (1994) Topical therapy of aging skin. J Geriatr Dermatol 2: 20–23

    Google Scholar 

  39. Bernstein EF, Uitto J (1995) Connective tissue alterations in photoaged skin and the effects of alpha hydroxy acids. J Geriatr Dermatol 3: 7A-18A

    Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University of Pennsylvania, School of Medicine, Rm 227 CRB, 415 Curie Blvd., 19104, Philadelphia, PA, USA

    Lorraine H. Kligman

  2. Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA

    Allen N. Sapadin & Elaine Schwartz

Authors
  1. Lorraine H. Kligman
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  2. Allen N. Sapadin
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  3. Elaine Schwartz
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Additional information

This study was supported in part by Ortho Pharmaceutical Corp. Dermatology Division, Raritan, N.J., USA

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Kligman, L.H., Sapadin, A.N. & Schwartz, E. Peeling agents and irritants, unlike tretinoin, do not stimulate collagen synthesis in the photoaged hairless mouse. Arch Dermatol Res 288, 615–620 (1996). https://doi.org/10.1007/BF02505265

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  • DOI: https://doi.org/10.1007/BF02505265

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