Archives of Dermatological Research

, Volume 295, Issue 6, pp 255–262 | Cite as

Separation of retinoid-induced epidermal and dermal thickening from skin irritation

  • James VaraniEmail author
  • Helene Fligiel
  • Jian Zhang
  • Muhammad Nadeem Aslam
  • Yi Lu
  • Lindsay A. Dehne
  • Evan T. Keller
Original Paper


The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9-cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all-trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.


Retinoids Epidermal hyperplasia Dermal thickening Irritation 



This study was supported in part by grants AR 49621 and DK 59169 from the USPHS. The authors would like to thank Molecular Design International, Inc. (MDI) of Memphis, TN, for supplying MDI-301.


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Copyright information

© Springer-Verlag is a part of Springer Sciences + Business Media 2003

Authors and Affiliations

  • James Varani
    • 1
    Email author
  • Helene Fligiel
    • 1
  • Jian Zhang
    • 1
  • Muhammad Nadeem Aslam
    • 1
  • Yi Lu
    • 1
    • 2
  • Lindsay A. Dehne
    • 1
  • Evan T. Keller
    • 1
  1. 1.Department of PathologyThe University of MichiganAnn ArborUSA
  2. 2.Department of ImmunologyTianjin Medical UniversityTianjinChina

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