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Volume 4
Clinical Pediatric Dermatology
ISSN: 2472-0143
Page 17
Notes:
October 15-16, 2018 Rome, Italy
&
JOINT EVENT
14
th
International Conference on
Clinical Dermatology
5
th
International Conference on
Advances in Skin, Wound Care and Tissue Science
Wound Congress 2018 &
Clinical Dermatology Congress 20
18
October 15-16, 2018
Ryan Moseley
Cardiff University, UK
Ryan Moseley, Clin Pediatr Dermatol 2018, Volume 4
DOI: 10.21767/2472-0143-C2-004
Development of epoxy-tigliane pharmaceuticals as novel therapeutics for dermal fibrosis
E
xcessive dermal scarring/fibrosis poses major challenges to Healthcare Services worldwide, confounded by existing
therapies being unsatisfactory at treating fibrosis. Therefore, there is significant need for novel anti-fibrotic therapies with
improved efficacy. We are evaluating the novel healing properties of epoxy-tiglianes (EBC-46, EBC-211), isolated from the
Fontain’s Blushwood Tree indigenous to Queensland’s tropical rainforest. EBC-46 possesses potent anti-cancer properties and
stimulates exceptional healing following tumour destruction, manifested as accelerated wound re-epithelialisation, closure
and minimal scarring. To elucidate their anti-scarring properties, we assessed epoxy-tigliane effects on fibroblast proliferation,
migration; and transforming growth factor-β1 (TGF-β1)-driven myofibroblast differentiation/behaviour. Dermal fibroblasts
were treated with EBC-46 or EBC-211 (0-10µg/ml). Cell cycle progression/proliferation were assessed by Flow Cytometry
and MTT assay. Migration was assessed using in vitro scratch wounds/Time-Lapse Microscopy. TGF-β1-driven, fibroblast-
myofibroblast differentiation was examined by immuno-cytochemical/QRT-PCR detection of α-smooth muscle actin
(α-SMA) expression/stress fibre formation. Epoxy-tigliane-induced gene expression changes were quantified by Microarrays,
confirmed by protein level analyses. Both epoxy-tiglianes significantly retarded fibroblast proliferation, although neither
affected migration. Although α-SMA expression/stress fibre organization and myofibroblast formation were unaffected at
0.001-0.01µg/ml or 1-10µg/ml EBC-46, EBC-46 significantly inhibited α-SMA expression/stress fibre formation at 0.1µg/ml,
with cells retaining normal fibroblast morphologies. EBC-211 induced similar effects at 10µg/ml. Epoxy-tiglianes up-regulated
proteinase, anti-fibrotic matrix component and TGF-β1 inhibitor genes; and down-regulated proteinase inhibitors, pro-fibrotic
matrix component and TGF-β1 signalling genes. Epoxy-tiglianes also increased high molecular weight hyaluronan synthesis.
Therefore, epoxy-tiglianes modulate fibroblast proliferation, differentiation and matrix composition/turnover, inducing scar
resolution. Findings support epoxy-tigliane development as novel anti-fibrotic therapeutics against dermal scarring/fibrosis.
Biography
Ryan Moseley graduated from Swansea University with a BSc (Honours) Degree in Biochemistry. Later, he obtained his PhD from the School of Dentistry, University of
Wales College of Medicine, examining the role of oxidative stress in periodontal disease. He continues his research at Cardiff University, where he is currently a Reader
in Tissue Repair and Director of the CITER MSc Programme in Tissue Engineering. He research focuses on the mechanisms underlying dermal and oral wound healing
during health and disease; and the development of stem cell, biomaterial and pharmaceutical based strategies to address impaired healing in these tissues. He has been
supported by funding bodies worldwide, including the MRC, NHMRC and Wellcome Trust, culminating in numerous published papers, filed patents with industrial partners
in the dermal wound healing sector (Convatec, Systagenix Wound Management, Peplin/LEO Pharma, QBiotics); and many conference prizes.
MoseleyR@cardiff.ac.uk