ArticleArchives of dermatological research1996
Regulation of keratinocyte proliferation and differentiation by all-trans-retinoic acid, 9-cis-retinoic acid and 1,25-dihydroxy vitamin D3.
Article in Archives of dermatological research, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 58 citations in OpenAlex.
- Assessing the relationship between vitamin D3 and stratum corneum hydration for the treatment of xerotic skin.Nutrients · 2012Trial
- Isolation, Culture, and Analyses of Keratinocytes, Fibroblasts, and Hair Follicles from Normal Human Skin and Cancer-Associated Fibroblasts from Skin Tumors.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Genomic regions occupied by both RARα and VDR are involved in the convergence and cooperation of retinoid and vitamin D signaling pathways.Nucleic acids research · 2025Article
- Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids.Biomolecules · 2024Article
- Growth modulatory effects of fenretinide encompass keratinocyte terminal differentiation: a favorable outcome for oral squamous cell carcinoma chemoprevention.Carcinogenesis · 2024Article
- The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review.International journal of molecular sciences · 2022Review
- Human saliva stimulates skin and oral wound healing in vitro.Journal of tissue engineering and regenerative medicine · 2019Article
- G2A AttenuatesAnnals of dermatology · 2017Article
- Formation of keratinocyte multilayers on filters under airlifted or submerged culture conditions in medium containing calcium, ascorbic acid, and keratinocyte growth factor.Histochemistry and cell biology · 2016Article
- A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells.Scientific reports · 2016Article
- Development of a Full-Thickness Human Gingiva Equivalent Constructed from Immortalized Keratinocytes and Fibroblasts.Tissue engineering. Part C, Methods · 2016Article
- Distinct expression patterns and roles of aldehyde dehydrogenases in normal oral mucosa keratinocytes: differential inhibitory effects of a pharmacological inhibitor and RNAi-mediated knockdown on cellular phenotype and epithelial morphology.Histochemistry and cell biology · 2013Article
- Toll-like receptors: role in dermatological disease.Mediators of inflammation · 2010Article
- Novel markers of early ovarian pre-granulosa cells are expressed in an Sry-like pattern.Developmental dynamics : an official publication of the American Association of Anatomists · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We studied the effect of all-trans retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) on proliferation and differentiation of human keratinocytes cultured in a submerged culture system for up to 5 weeks and evaluated changes in cell morphology and in the expression of proliferation- and terminal differentiation-related genes on both the mRNA and the protein levels. Under control culture conditions, the expression of small proline-rich proteins (SPRR1 and SPRR2), involucrin, Ki67 and c-jun reached a maximum after 2 weeks in culture (1 week postconfluence) and then decreased as the tissue architecture of the cultures deteriorated. Upon simultaneous treatment with both retinoids and 1,25(OH)2D3 a culture was generated that remained stable for 4 weeks with at least eight living cell layers. Furthermore, this culture showed a pattern of SPRR2 and involucrin expression which closely resembled that of native epidermis, a maintained Ki67 expression and a strongly induced c-jun expression. Treatment with 1,25(OH)2D3 alone inhibited cell proliferation and stimulated cell differentiation resulting in acceleration of the differentiated phenotype and was accompanied by inhibition of c-jun and Ki67 expression and also, surprisingly by inhibition of SPRR1, SPRR2 and involucrin expression. In contrast, treatment with all-trans-RA and/or 9-cis-RA induced a more proliferative phenotype with a prolonged lifespan as compared to control cultures. SPRR1 was weakly repressed, SPRR2 was strongly repressed, a delayed induction of involucrin occurred, and c-jun and Ki67 expression were maintained. These results show that modulation of the composition of the medium by the addition of various vitamins results in changes in the balance between keratinocyte proliferation and differentiation which correspond to changes in the expression of proliferation and differentiation markers and prolongation of the culture lifespan.
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