Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin
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Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin. / Meier, Natalia T; Haslam, Iain S; Pattwell, David M; Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Eike Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E; Hardman, Matthew J; Paus, Ralf.
In: PLOS ONE, Vol. 8, No. 9, 01.01.2013, p. e73596.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -