Triterpenes promote keratinocyte differentiation in vitro, ex vivo and in vivo: a role for the transient receptor potential canonical (subtype) 6.
It has been shown recently that triterpenes inhibit cancer cell growth of various cell types in vitro. In this work, the effect of highly purified triterpenes (TE) with betulin as the major compound (>80% w/w) on cell proliferation, apoptosis, and differentiation of human keratinocytes was analyzed in vitro, ex vivo, and in vivo. In vitro, TE increased calcium influx into primary keratinocytes and upregulated various differentiation markers including keratin 10. TE also specifically increased the expression of the non-selective transient receptor potential canonical (subtype) 6 (TRPC6) in keratinocytes, and knocking down TRPC6 inhibited keratin 10 upregulation. Ex vivo, in human skin explants TE induced the expression of TRPC6 in the epidermis and increased DNA fragmentation of terminally differentiating keratinocytes. Topical treatment with TE of actinic keratoses, that represent in situ squamous cell carcinomas with disturbed epithelial differentiation, resulted in downgrading of aberrant Ki67 expression and upregulation of keratin 10 in vivo. Our data indicate that TE promotes keratinocyte differentiation in vitro and in vivo. This effect seems to be mediated at least in part by TRPC6.
Woelfle
Ute
U
Department of Dermatology, Competence Center skintegral, University Medical Center Freiburg, Germany.
Laszczyk
Melanie N
MN
Kraus
Margarethe
M
Leuner
Kristina
K
Kersten
Astrid
A
Simon-Haarhaus
Birgit
B
Scheffler
Armin
A
Martin
Stefan F
SF
Müller
Walter E
WE
Nashan
Dorothee
D
Schempp
Christoph M
CM
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D053550:Keratin-10 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D034741:RNA, Small Interfering; D012878:Skin Neoplasms / Q000188:drug therapy; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism; D000074287:TRPC6 Cation Channel; D014315:Triterpenes / Q000494:pharmacology*
C507493:KRT10 protein, human; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D014315:Triterpenes; D053550:Keratin-10; D002118:Calcium