Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin

Sunil Nagpal, Sheetal Patel, Heidi Jacobe, Daniel DiSepio, Corine Ghosn, Monica Malhotra, Min Teng, Madeleine Duvic, Roshantha A S Chandraratna

Research output: Contribution to journalArticle

188 Scopus citations

Abstract

Retinoids exert their biologic effects through two families of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which belong to the superfamily of steroid/thyroid hormone nuclear receptors. By using a subtraction hybridization approach, we have identified a cDNA sequence TIG2 (Tazarotene-induced gene 2), whose expression is up-regulated by the treatment of skin raft cultures by an RAR β/γ-selective anti- psoriatic synthetic retinoid tazarotene (AGN 190168/ethyl 6-[2-(4,4- dimethylthiochroman-6-yl)-ethynyl] nicotinate). The retinoid-mediated up- regulation in the expression of TIG2 was confirmed by Northern blot analysis. Upon sequencing, TIG2 was found to be a cDNA whose complete sequence was not in the GenBank and EMBL data bases. The TIG2 cDNA is 830 bp long and encodes a putative protein product of 164 amino acids. TIG2 is neither expressed nor induced by tazarotene in primary keratinocyte and fibroblast cultures. Thus, TIG2 is expressed and induced by tazarotene only when keratinocytes and fibroblasts form a tissue-like 3-dimensional structure. We further demonstrate that RAR-specific retinoids increase TIG2 mRNA levels. In contrast, neither RXR-specific retinoids nor 1,25-dihydroxyvitamin D3 increased TIG2 levels. Finally, we demonstrate that TIG2 is expressed at high levels in nonlesional psoriatic skin but at lower levels in the psoriatic lesion and that its expression is up-regulated in psoriatic lesions after topical application of tazarotene.

Original languageEnglish (US)
Pages (from-to)91-95
Number of pages5
JournalJournal of Investigative Dermatology
Volume109
Issue number1
DOIs
StatePublished - Jan 1 1997

Keywords

  • Psoriasis
  • Retinoic acid receptor
  • Subtractive hybridization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Nagpal, S., Patel, S., Jacobe, H., DiSepio, D., Ghosn, C., Malhotra, M., Teng, M., Duvic, M., & Chandraratna, R. A. S. (1997). Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. Journal of Investigative Dermatology, 109(1), 91-95. https://doi.org/10.1111/1523-1747.ep12276660