Androgens modulate keratinocyte differentiation indirectly through enhancing growth factor production from dermal fibroblasts
| Autor: | Saaya Koike, Kenshi Yamasaki, Setsuya Aiba, Chanat Kumtornrut, Takeshi Yamauchi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Keratinocytes medicine.medical_specialty medicine.drug_class medicine.medical_treatment Dermatology Cell Communication Fibroblast growth factor Biochemistry Epiregulin Cell Line 030207 dermatology & venereal diseases 03 medical and health sciences Cytokeratin Sebaceous Glands 0302 clinical medicine Amphiregulin Internal medicine Acne Vulgaris medicine Humans Molecular Biology Acne Cells Cultured FGF10 integumentary system Chemistry Growth factor Gene Expression Profiling Cell Differentiation Fibroblasts medicine.disease Androgen Coculture Techniques Sebum 030104 developmental biology Endocrinology Androgens Intercellular Signaling Peptides and Proteins Hair Follicle |
| Zdroj: | Journal of dermatological science. 93(3) |
| ISSN: | 1873-569X |
| Popis: | Background The main pathogenesis of acne vulgaris is increase in sebum production and abnormal keratinization of the hair infundibulum. The androgens are involved in acne pathogenesis by modulating sebaceous glands to enhance sebum production. However, the molecular mechanisms of abnormal keratinization of the hair infundibulum are not fully elucidated. Objective We hypothesized that the androgens affect the dermal fibroblasts, another androgen receptor-positive cells in the skin, resulting in abnormal keratinization through keratinocyte-fibroblast interaction. Methods We investigated effects of androgens and estrogens on growth factors expressions by RT-PCR and western blot analysis in human fibroblast (hFB), human keratinocyte (hKC), and fibroblast-keratinocyte co-culture. In vivo, we examined the growth factor expression in acne lesions compared to normal hair follicles by laser-assisted confocal microscope. Results In vitro, androgens but not estrogens significantly increased amphiregulin (AREG), epiregulin (EREG), fibroblast growth factor (FGF) 10, and insulin-like growth factor binding protein (IGFBP) 5 mRNA and protein expressions in human fibroblasts but not in keratinocytes. In vivo, AREG, EREG, FGF10, and IGFBP5 were more abundant in acne lesion compared to normal facial skin. FGF10 suppressed cytokeratin 1 and cytokeratin 10 expression in hKC, which was along with the decreased ratio of cytokeratin 10 against cytokeratin 14 in acne lesions compared to normal facial skin. Also, DHT suppressed cytokeratin 1 and cytokeratin 10, in fibroblast-keratinocyte co-culture similarly to the effect of FGF10 to hKC. Conclusion These observations suggested that androgens enhance growth factors production from dermal fibroblasts, and growth factors from fibroblasts alter keratinocyte differentiation in acne lesion. |
| Databáze: | OpenAIRE |
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