Molecular Biology Reports

, Volume 20, Issue 2, pp 75–83 | Cite as

A retinoic acid-inducible skin-specific gene (RIS-1/psoriasin): molecular cloning and analysis of gene expression in human skinin vivo and cultured skin cellsin vitro

  • Amir Tavakkol
  • Christos C. Zouboulis
  • Elizabeth A. Duell
  • John J. Voorhees
Research Articles


A retinoic acid (RA) inducible skin-specific gene transcript (RIS-1) was isolated by differential hybridization screening of a RA-treated human skin cDNA library. The library was constructed from pooled RNA derived from normal adult human skin treated with alltrans-RA for 4 h (n=6) and 12 h (n=6)in vivo. RIS-1 cDNA corresponded to a 0.6 kb transcript that was barely detectable in normal adult human skin but was significantly induced by 8 h in RA-treated compared to vehicle-treated skin (range 1.1–3.6 fold). Prolonged RA treatment for up to 24 h further increased relative RIS-1 mRNA levels by 1.3–5.5 fold. HPLC analysis of the RA content of 0.1% RA-treated skinin vivo revealed significant levels at 6 h (18.8–120.6 ng RA/g wet weight tissue; approximately 240 nM), immediately preceding the time point at which the increased RIS-1 mRNA level was first seen. This concentration of RA also induced the mRNA levels for cellular RA binding protein II (1.6–19 fold), a marker of RA activity in human skin. RIS-1 mRNA was detected by Northern and dot blotting only in normal skin but not in any other normal human tissues examined, indicating a tissue-specific pattern of gene expression. RIS-1 transcripts were detected at very low levels in untreated cultured human epidermal keratinocytes, while no expression was seen in dermal fibroblasts and melanocytes, the other major cell types in skin. Southern analysis of human and mouse DNA indicated the existence of evolutionarily conserved sequences for RIS-1 between these two species. The polypeptide sequence derived from the partial RIS-1 cDNA was found to be identical to the calcium binding domain found in ‘psoriasin’, a gene whose expression appears to be increased in the skin of psoriasis patients.

Key words

retinoic acid skin differential hybridization cloning keratinocytes gene expression 



retinoci acid-inducibleskin-specific gene


All-trans retinoic acid


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fisher JG, Esmann J, Griffiths CEM, Talwar HS, Duell EA, Hammerberg C, Elder JT, Karabin GD, Nickoloff BJ, Cooper KD & Voorhees JJ (1991) J. Invest. Dermatol. 96: 699–707.Google Scholar
  2. 2.
    Saurat J-H (1989) in: Pharmacology of Retinoids in Skin (Reichert U and Shroot B, eds), vol. 3, pp. 215–226, Basel, KragerGoogle Scholar
  3. 3.
    Petkovich M, Brand NJ, Krust A & Chambon P (1987) Nature 330: 444–450Google Scholar
  4. 4.
    Gigueref V, Ong ES, Segui P & Evans RM (1987) Nature 330: 624–629Google Scholar
  5. 5.
    Hoffmann B., Lehmann JM, Zhang XK, Hermann T, Husmann M, Graupner G & Pfahl M (1990) Mol. Endo. 4, 1727–1736Google Scholar
  6. 6.
    Dolle P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas IJ & Chambon P (1989) Nature 342, 702–705Google Scholar
  7. 7.
    Tavakkol A, Griffiths CEM, Keane KM, Palmer RD & Voorhees JJ (1992) J. Invest. Dermatol. 99, 146–150Google Scholar
  8. 8.
    Redfern CPF & Todd C (1992) J Cell Sci. 102, 113–121Google Scholar
  9. 9.
    Elder JT, Åström A, Tavakkol A, Krust A, Kastner P, Chambon P & Voorhees JJ (1992) J. Invest. Dermatol. 98, 36S-41SGoogle Scholar
  10. 10.
    Ong DE & Chytil F (1978) J. Biol. Chem. 253, 4551–4554Google Scholar
  11. 11.
    Nilsson MHL, Spurr NK, Saksena P, Busch C, Norlinder H, Peterson PA & Sundelin J (1988) Biochemistry 173, 45–51Google Scholar
  12. 12.
    Åström A, Tavakkol A, Peterson U, Cromie M, Elder JT & Voorhees JJ (1991) J Biol Chem 266, 17662–17666Google Scholar
  13. 13.
    Eller MS, Oleksiak MF, McQuaid TJ, McAfee SG & Gilchrest BA (1992) Exp. Cell. Res. 199, 328–336Google Scholar
  14. 14.
    Reynolds NJ, Fisher GJ, Griffiths CEM, Tavakkol A, Talwar HS, Rowse PE, Hamilton TA & Voorhees JJ (1993) J. Pharmacol. Exp. Therap. 266, 1636–1642Google Scholar
  15. 15.
    Maden M, Ong DE, Summerbell D & Chytyl F (1988) Nature 335, 733–735Google Scholar
  16. 16.
    Bedo G, Santisteban P & Aranda A (1989) Nature (London) 339, 231–234Google Scholar
  17. 17.
    Lucas PC, O'Brein RM, Mitchell JA, Davis CM, Imai E, Forman BM, Samuels HH & Granner DK (1991) Proc. Natl. Acad. Sci. USA 88, 2184–2188Google Scholar
  18. 18.
    LaRosa GJ & Gudas LJ (1988) Proc. Natl. Acad. Sci. USA, 85, 329–333Google Scholar
  19. 19.
    Duester G, Shean MI, McBride MS & Stewart MJ (1991) Mol. Cell. Biol. 11, 1638–1646Google Scholar
  20. 20.
    Gudas LJ (1992) Cell Growth Diff 3, 652–662Google Scholar
  21. 21.
    Duell ED, Åström A, Griffiths CEM, Chambon P & Voorhees JJ (1992) J. Clin. Invest. 90, 1269–1274Google Scholar
  22. 22.
    Lowry OH, Rosebrough NJ, Farr AL & Randall RJ (1951) J. Biol. Chem. 193, 265–275Google Scholar
  23. 23.
    Zouboulis CC & Tavakkol A (1994) BioTechniques 16, 290–294Google Scholar
  24. 24.
    Laborda, J (1991) Nucl. Acids Res. 19, 3998Google Scholar
  25. 25.
    Danielson PE, Forss-Petter S, Brow MA, Calavetta L, Douglass J, Milner RJ & Sutcliffe JG (1988) DNA 7, 261–267Google Scholar
  26. 26.
    Gonzalez IL, Gorski JL, Campen TJ, Dorney DJ, Erickson JM, Sylvestor JE & Schmickel RD (1985) Proc. Natl. Acad. Sci. USA 82, 7666–7670Google Scholar
  27. 27.
    Sambrook J, Fritsch EF & Maniatis T (1989) Molecular Cloning: A laboratory Manual, 2nd Ed., (Cold Spring Harbor, New YorkGoogle Scholar
  28. 28.
    Elder JT, Cromie M, Griffiths CEM, Chambon P & Voorhees JJ (1993) J Invest Dermatol 100, 356–359Google Scholar
  29. 29.
    Madsen P, Rasmussen HH, Leffers H, Honore B, Dejgaard K, Olsen E, Kiil J, Walbum E, Anderson AH, Basse B, Lauridsen JB, Ratz GP, Celis A, Vandekerckhove J & Celis JE (1991) J. Invest. Dermatol. 97, 701–712Google Scholar
  30. 30.
    Kretsinger RH (1987) Cold Spring Harbor Symposia on Quantitative Biology 52, 499–510Google Scholar
  31. 31.
    Durand B, Saunders M, Leroy P, Leid M & Chambon P (1992) Cell 71, 73–85Google Scholar
  32. 32.
    Anger T (1991) Contact Dermatitis 25, 108–114Google Scholar
  33. 33.
    Proksch E, Feingold KR, Mao-Qiang M & Elias PM (1991) J. Clin. Invest. 87, 1668–1673Google Scholar
  34. 34.
    Marks R, Hill S & Barton SP (1990) Br. J. Dermatol. 123, 457–466Google Scholar
  35. 35.
    Kodomatsu K, Tomokura M & Muramatsu T (1988) Biochem. Biophys. Res. Commun. 151, 1312–1316Google Scholar
  36. 36.
    Suva II, Ernst M & Rodan GA (1991) Mol. Cell. Biol. 5, 2503–2510Google Scholar
  37. 37.
    Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WJ, Hunter T & Karin M (1988) Nature 332, 166–171Google Scholar
  38. 38.
    Sitzmann J, Algermissen B, Czarnetzki BM & LeMotte P (1993) J. Invest. Dermatol. 100, 220Google Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Amir Tavakkol
    • 1
  • Christos C. Zouboulis
    • 1
  • Elizabeth A. Duell
    • 1
  • John J. Voorhees
    • 1
  1. 1.Department of DermatologyUniversity of Michigan Medical CenterAnn ArborUSA

Personalised recommendations