Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo

Guo You Zhang, Ewan A. Langan, Natalia T. Meier, Wolfgang Funk, Frank Siemers, Ralf Paus

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

There is a pressing need for improved preclinical model systems in which to study human skin wound healing. Here, we report the development and application of a serum-free full thickness human skin wound healing model. Not only can re-epithelialization (epidermal repair) and angiogenesis be studied in this simple and instructive model, but the model can also be used to identify clinically relevant wound-healing promoting agents, and to dissect underlying candidate mechanisms of action in the target tissue. We present preliminary ex vivo data to suggest that Thyroxine (T4), which reportedly promotes skin wound healing in rodents in vivo, may promote key features of human skin wound healing. Namely, T4 stimulates re-epithelialisation and angiogenesis, and modulates both wound healing-associated epidermal keratin expression and energy metabolism in experimentally wound human skin. Functionally, the wound healing-promoting effects of T4 are at least partially mediated via fibroblast growth factor/fibroblast growth factor receptor-mediated signalling, since they could be significantly antagonized by bFGF-neutralizing antibody. Thus, this pragmatic, easy-to-use full-thickness human skin wound healing model provides a useful preclinical research tool in the search for clinically relevant candidate wound healing-promoting agents. These ex vivo data encourage further pre-clinical testing of topical T4 as a cost-efficient, novel agent in the management of chronic human skin wounds.

Original languageEnglish (US)
Article numbere0212659
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2019

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Re-Epithelialization
L-thyroxine
thyroxine
angiogenesis
tissue repair
Thyroxine
skin (animal)
Wound Healing
Skin
animal injuries
Fibroblast Growth Factor Receptors
Fibroblast Growth Factors
Keratins
Neutralizing Antibodies
fibroblast growth factors
keratin
Wounds and Injuries
Repair
neutralizing antibodies
energy metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo. / Zhang, Guo You; Langan, Ewan A.; Meier, Natalia T.; Funk, Wolfgang; Siemers, Frank; Paus, Ralf.

In: PloS one, Vol. 14, No. 3, e0212659, 01.03.2019.

Research output: Contribution to journalArticle

Zhang, Guo You ; Langan, Ewan A. ; Meier, Natalia T. ; Funk, Wolfgang ; Siemers, Frank ; Paus, Ralf. / Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo. In: PloS one. 2019 ; Vol. 14, No. 3.
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