Journal Article

Thyrotropin-Releasing Hormone (TRH) Promotes Wound Re-Epithelialisation in Frog and Human Skin

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

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Amphibia / Amphibians / Animals / Apoptosis - drug effects / Biology / Biopsy / Cell Differentiation - drug effects / Cell Proliferation - drug effects / Cytokeratin / Dermatology / Epidermis / Epithelium - drug effects / Epithelium - metabolism / Estrogens - pharmacology / Evolution, Molecular / Exploration / Female / Frogs / Gene expression / Genetic aspects / Genomes / Growth factors / Healing / Humans / Inflammation / Keratin-6 - metabolism / Life sciences / Male / Middle Aged / Organ culture / Physiological aspects / Protein Precursors - metabolism / Re-Epithelialization - drug effects / Regeneration / Reptiles & amphibians / Serum - metabolism / Skin / Skin - cytology / Skin - drug effects / Skin - metabolism / Studies / Thyroid gland / Thyroid-stimulating hormone / Thyrotropin / Thyrotropin-releasing hormone / Thyrotropin-Releasing Hormone - pharmacology / Up-Regulation - drug effects / Wound healing / Xenopus / Xenopus laevis