Retinoids and Keratinocyte Differentiation in vitro

Abstract

Standard retinoids (e.g. etretinate, isotretinoin) are successful in the treatment of a variety of dermatological disorders. However, they are handicapped by an unfavorable ratio between activity and toxicity. In order to find more successful substances new promising compounds were recently synthesized. The aim of this study was to screen new monoaro-mates (etretin (Ro 10–1670) , demethyletretin (Ro 12–7310), 13-cis-etretin(Ro 13–7652) and the polyaromates arotinoid (Ro 15–0778), arotinoid acid (Ro 13–7410) and arotinoid ethyl sulfone (Ro 15–1570) for their effect on keratinocyte differentiation in vitro and to compare these results with differentiation data of retinoids currently used clinically. It was found that the second generation of retinoids had a lower antikeratinizing potential than the third generation of retinoids. They markedly inhibited crosslinked keratins and envelope proteins. Arotinoid acid was found to be the most potent derivative. In contrast to this, differences with regard to the synthesis of keratohyalingranule macroaggregates were detected between the retinoid derivatives. Arotinoid acid and arotinoid sulfone stimulated this protein fraction, whereas arotinoid left this fraction uninfluenced. If the data obtained were considered the selection criterion for the future therapeutic application of the new arotinoids in psoriasis therapy, it should be more useful to employ arotinoid acid or arotinoid sulfone rather than arotinoid in clinical psoriasis studies.

Pathogenesis and Pathogenesis Related Treatment of Acne

“…Tretinoin via the topical route and isotretinoin mostly via the systemic route reduce the number of comedones and of microcomedones. Both drugs are capable of modulating keratin filament macroaggregates, as has been shown in keratinocytes in vitro (37). Tretinoin stimulates the mitotic activity within the follicle, which leads to an increased turn-Over of the infundibulum corneocytes and to the expulsion of the comedo (38).…”

Retinoids Strongly and Selectively Correlate With Keratin 13 and Not Keratin 19 Expression in Cutaneous Warts of Renal Transplant Recipients

“…Retinoids, by inducing K13 expression or directing keratinocytes toward (esophageal) differentiation, might be chemopreventive by "freezing" cells in this differentiated state and preventing them from (further) dedifferentiating. Results of previous studies 6,23,24 of retinoid effects on epidermal keratinocytes have shown that in response to retinoid treatment, higher molecular weight keratins, typically encountered in squamous epithelia, disappear, and synthesis of 2 new low molecular-weight keratins, a 40-and a 52-kd keratin, corresponding to K19 and K13, respectively, is enhanced. In the absence of vitamin A, the opposite occurs, with an enhanced terminal epidermal type of differentiation.…”

Acitretin Use in Dermatology

“…1,3 Acitretin binds strongly to cellular retinoic acid binding protein (CRABP), which transports retinoic acid from the cytosol to the nucleus. 4 It modifies gene transcription of over 500 genes, 5 reduces proliferation, and increases keratinocyte differentiation, 6 inhibiting interleukin 6 (IL-6)–driven induction of T helper-17 (Th-17) cells and promoting differentiation of T regulatory cells. 7 Acitretin inhibits keratinocyte production of vascular endothelial growth factor 8 and inhibits neutrophil migration.…”