title: Application of cantharidin or 12-O-tetradecanoylphorbol-13-acetate on mouse epidermis induces a cell population shift that causes altered keratin distribution.
abstract: The tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) causes changes in epidermal protein expression, especially in the major differentiation products keratins K1 and K10. These keratins and filaggrin were studied in a pulse-labelled cell cohort in hairless mouse epidermis stimulated to proliferate by TPA or the hyperplasiogen cantharidin. Cells in DNA synthesis were pulse-labelled by 5-bromo-2-deoxyuridine (BrdU) 16 h after topical application of cantharidin or TPA. The BrdU-labelled cell cohort, the two keratins, and filaggrin were spatially mapped by paired immunofluorescence staining. Both cantharidin- and TPA-treated epidermis displayed altered distributions of K1 and K10 with expression only in the outermost cell layers, but the start of their postreplicative expression paralleled that in normal epidermis (18 h for K1 and 24 h for K10 after the last round of DNA synthesis). Cantharidin- and TPA-induced epidermal hyperplasia showed increased basal cell proliferation, accelerated suprabasal migration, and shortened transit time. Thus, the newly formed hyperplastic epidermis was composed of keratinocytes with a lower mean cellular age than that seen in unperturbed epidermis, which caused altered distribution of K1 and K10. Both hyperplastic and normal epidermis showed filaggrin expression in stratum granulosum; this started earlier in treated (30-36 h) than in untreated (96 h) skin. We concluded that the postmitotic onset of K1 and K10 expression was unaltered in regenerative epidermis, whereas filaggrin expression was considerably accelerated and thus influenced by the cell kinetic changes.
authors.affiliation: Institute of Pathology, University of Oslo, National Hospital, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Heyden
authors.forename: C
authors.initials: C
authors.lastname: Lützow-Holm
authors.forename: O P
authors.initials: OP
authors.lastname: Clausen
authors.forename: E V
authors.initials: EV
authors.lastname: Thrane
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: D R
authors.initials: DR
authors.lastname: Roop
authors.forename: S H
authors.initials: SH
authors.lastname: Yuspa
authors.forename: H S
authors.initials: HS
authors.lastname: Huitfeldt
mesh_terms: D000818:Animals; D002193:Cantharidin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects*; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000032:analysis; D007633:Keratins / Q000032:analysis*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D011493:Protein Kinase C / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007633:Keratins; D011493:Protein Kinase C; D002193:Cantharidin; D013755:Tetradecanoylphorbol Acetate