Retinoid-responsive transcriptional changes in epidermal keratinocytes
Lee DD, Stojadinovic O, Krzyzanowska A, Vouthounis C, Blumenberg M, Tomic-Canic M.
J Cell Physiol, 2009, 220, 427-439
Retinoids play a major role in regulating growth, differentiation and apoptosis of many cell types, including keratinocytes, fibroblasts and sebocytes. The molecular mechanisms mediating these effects involve binding of the retinoid to ligand-activated nuclear hormone receptors forming dimers and subsequent binding to specific DNA sequences called retinoic acid response elements (RARFs) to regulate target genes [11. Therapeutic uses of retinoids include treatment of psoriasis, acne and some preneoplastic lesions and cancers [21. These benefits are limited by the side effects of scaling, erythema and dryness. The most efficacious acne treatment, 13-cis retinoic acid (RA) or Roaccutane[R], is well known for causing considerable improvement in very severe acne conditions (for example acne conglobata) but usage is also limited by its potential teratogenic effects. Therefore, it would be advantageous to be able to design retinoids which have the profound beneficial effects of retinoid treatment, while designing out the negative effects. Extensive work on identifying such retinoid compounds has not been successful to date. Understanding the downstream effects transduced by retinoids activating their receptors might help to provide insights into how better to develop such compounds and this study was designed to comprehensively define the transcriptional targets regulated by retinoids in human epidermal...