Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin.

Natalia T. Meier, Iain S. Haslam, David M. Pattwell, Guo You Zhang, Vladimir Emelianov, Roberto Paredes, Sebastian Debus, Matthias Augustin, Wolfgang Funk, Enrique Amaya, Jennifer E. Kloepper, Matthew J. Hardman, Ralf Paus

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30 Citations (Scopus)

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.

Original languageEnglish
Article numbere73596
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - 2 Sep 2013
Externally publishedYes

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    Meier, N. T., Haslam, I. S., Pattwell, D. M., Zhang, G. Y., Emelianov, V., Paredes, R., Debus, S., Augustin, M., Funk, W., Amaya, E., Kloepper, J. E., Hardman, M. J., & Paus, R. (2013). Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin. PLoS One, 8(9), [e73596]. https://doi.org/10.1371/journal.pone.0073596