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

TY - JOUR

T1 - Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

AU - Meier, Natalia T

AU - Haslam, Iain S

AU - Pattwell, David M

AU - Zhang, Guo-You

AU - Emelianov, Vladimir

AU - Paredes, Roberto

AU - Debus, Eike Sebastian

AU - Augustin, Matthias

AU - Funk, Wolfgang

AU - Amaya, Enrique

AU - Kloepper, Jennifer E

AU - Hardman, Matthew J

AU - Paus, Ralf

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Aged

KW - Animals

KW - Apoptosis

KW - Cell Differentiation

KW - Cell Proliferation

KW - Epithelium

KW - Estrogens

KW - Evolution, Molecular

KW - Female

KW - Humans

KW - Keratin-6

KW - Male

KW - Middle Aged

KW - Protein Precursors

KW - Re-Epithelialization

KW - Serum

KW - Skin

KW - Thyrotropin-Releasing Hormone

KW - Up-Regulation

KW - Xenopus

U2 - 10.1371/journal.pone.0073596

DO - 10.1371/journal.pone.0073596

M3 - SCORING: Journal article

C2 - 24023889

VL - 8

SP - e73596

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 9

ER -