Oral Presentation 2015 Annual Meeting of the Australasian Society for Dermatology Research

rLRRFIP-1, a novel therapy approach for improved wound healing (#14)

Zlatko Kopecki 1 2 , Gink N Yang 1 , Stuart Mills 1 , Damian Adams 1 , Allison Cowin 1 2
  1. University of South Australia, Adelaide, SA, Australia
  2. Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia

Wound healing disorders are a therapeutic problem of increasing clinical importance involving substantial morbidity, mortality, and rising health care costs and this is particularly significant for our elderly population. Our studies, investigating the Leucine Rich Repeat Flightless Interacting Protein -1 (LRRFIP1), an important regulator of TLR mediated inflammation and cytokine secretion, now reveal a novel role for LRRFIP1 in mediating improved wound healing outcomes. LRRFIP1 directly associates with Flightless I (Flii) and significantly increases keratinocyte and fibroblast proliferation and cellular migration in-vitro. Using wild-type mice we investigated the effect of intradermal rLRRFIP1 injections (1mg/ml and 10mg/ml) on wound healing outcomes. We show that rLRRFIP1 reduced Flii expression in wounds in-vivo and resulted in significantly improved healing with decreased macroscopic and microscopic wound area and gape observed at day 3 and 7 post wounding. Wounds treated with rLRRFIP1 also showed increased numbers of proliferative fibroblasts corresponding with increased Collagen I and Collagen III expression in these wounds. Increased levels of rLRRFIP1 in wound in-vivo dampened TLR4 mediated inflammatory responses with significantly decreased number of early (MRP-14+ve) and late (F4/80+ve) macrophages present at day 7 post wounding. Decreased levels of TGF-β1 and increased levels of TGF-β3 were observed in rLRRFIP1 treated wounds at day 3 and 7 respectively suggesting a possible anti-scarring effect of rLRRFIP1. Further studies are required to elucidate if the mechanism behind LRRFIP1 action in wound healing are independent of Flii however these results identify rLRRFIP1 as a possible treatment modality for improved healing of wounds.