Altered Proliferation, Synthetic Activity, and Differentiation of Cultured Human sebocytes in the Absence of Vitamin A and Their Modulation by Synthetic Retinoids

Christos C Zouboulis, Bernhard P Korge, Dietmar Mischke, Constantin E Orfanos
1993 Journal of Investigative Dermatology  
Human sebocytes maintained in medium containing delipidized serum were studied for ultrastructural characteristics, cell proliferation, lipid synthesis, immunophenotype, and keratin expression before and after the addition of the synthetic retinoids isotretinoin and acitretin (10-8 -10-5 M). Compared to the properties of sebocytes cultured in normal sebocyte medium (1-2 X 10-7 M vitamin A), the use of delipidized serum (undetectable amounts of vitamin A) resui ted in prominent decrease of i)
more » ... liferation; ii) number of intracellular lipid droplets and synthesis of total lipids, especially triglycerides, squalene, and wax esters; and iii) labeling with monoclonal antibodies identifying progressive and latestage sebocyte differentiation. Intercellular spaces narrowed and cell-to-cell contacts were established by abundant desmosomes. Lanosterol was induced. Keratins 14, 16, 17, and 18 were upregulated and the keratin 16: keratin 4 ratio, negatively correlating with sebocyte differentiation, increased. Addition of isotretinoin and acitretin exerted a biphasic E vidence for control of epithelial differentiation by vitamin A dates back to the 1920s [1,2] . These original observations that vitamin A deficiency causes hyperkeratinization of the skin and induces squamous metaplasia and keratinization in many internal epithelia were followed by an equally important observation that excess of vitamin A inhibits keratinization of chick embryo skin and transforms it into a mucous-secreting epithelium [3]. Numerous illllitro studies showed that vitamin A and synthetic retinoids enhance proliferation and desquamation of cultured epidermal cells and suppress their differentiation, confirming the clinical observations [4][5][6]. Despite the abundant data concerning the epidermis, there is little Manuscript
doi:10.1111/1523-1747.ep12366092 pmid:8409536 fatcat:izgjr5uke5ghzjrdsls3pogpua