title: Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin.
abstract: There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.
authors.affiliation: Department of Dermatology, University of Luebeck, Luebeck, Germany ; Department of Pathology, University of Luebeck, Luebeck, Germany.
authors.forename: Natalia T
authors.initials: NT
authors.lastname: Meier
authors.forename: Iain S
authors.initials: IS
authors.lastname: Haslam
authors.forename: David M
authors.initials: DM
authors.lastname: Pattwell
authors.forename: Guo-You
authors.initials: GY
authors.lastname: Zhang
authors.forename: Vladimir
authors.initials: V
authors.lastname: Emelianov
authors.forename: Roberto
authors.initials: R
authors.lastname: Paredes
authors.forename: Sebastian
authors.initials: S
authors.lastname: Debus
authors.forename: Matthias
authors.initials: M
authors.lastname: Augustin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Funk
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Kloepper
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hardman
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D053553:Keratin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism; D062326:Re-Epithelialization / Q000187:drug effects*; D044967:Serum / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014981:Xenopus
chemical_list: D004967:Estrogens; D053553:Keratin-6; D011498:Protein Precursors; D013973:Thyrotropin-Releasing Hormone; C032253:involucrin
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