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

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

Sensory innervation of masseter, temporal and lateral pterygoid muscles in common marmosets

Abstract Myogenous temporomandibular disorders is associated with an increased responsiveness of nerves innervating the masseter (MM), temporal (TM), and lateral pterygoid muscles (LPM). This study aimed to examine sensory nerve types innervating MM, TM and LPM of adult non-human primate—common marmosets. Sensory nerves were localized in specific regions of these muscles. Pgp9.5, marker for all nerves, and NFH, a marker for A-fibers, showed that masticatory muscles were primarily innervated with A-fibers. The proportion of C- to A-fibers was highest in LPM, and lowest in MM. All C-fibers (pgp9.5+/NFH-) observed in masticatory muscles were peptidergic (CGRP+) and lacked mrgprD and CHRNA3, a silent nociceptive marker. TrpV1 was register in 17% of LPM nerves. All fibers in masticatory muscles were labeled with GFAP+, a myelin sheath marker. There were substantially more peptidergic A-fibers (CGRP+/NFH+) in TM and LPM compared to MM. MM, TM and LPM NFH+ fibers contained different percentages of trkC+ and parvalbumin+, but not trkB+ fibers. Tyrosine hydroxylase antibodies, which did not label TG, highlighted sympathetic fibers around blood vessels of the masticatory muscles. Overall, masticatory muscle types of marmosets have similarities and differences in innervation patterns