044 Adenoviral Gene Transfer of IL‐10 Differentially Regulates Hyaluronic Acid Synthase 1: Implications for Scarless Wound Healing

Introduction. We have demonstrated that wounds treated with adenoviral overexpression of Il-10 (AdIl-10) heal scarlessly, resembling fetal wound healing. Hyaluronic acid (HA) is elevated in fetal wounds. We hypothesized that IL-10 creates a permissive environment for scarless healing through the differential mediation of hyaluronic acid synthases (Has1–3). Methods. Adult C57 mice (n = 24) were pretreated with 5 × 108 PFU AdIL-10, AdLacz, or PBS. 48 hrs post-injection, 2-cm incisional wounds were created at the site of injection. Wounds harvested at 1, 3, and 5 days were analyzed for mRNA transcript levels of Has 1–3 and GAPDH via RT-PCR and band densitometry. Data expressed as signal intensity ratio relative to GAPDH ± SEM. Results. The three Has transcripts were expressed after pre-treatment and wounding at day 1, 3, and 5. At day 1, there is no significant difference in Has mRNA levels. At Day 3, Has1 transcript levels are significantly decreased in AdIl-10 treated wounds vs. controls. (Il-10 0.28 ± 0.04; LacZ 0.53 ± 0.06; PBS 0.43 ± 0.43, p < 0.005) At Day 5, there was a significant increase in Has1 transcript levels in AdIl-10 treated wounds compared to controls. (Il-10 0.82 ± 0.08; LacZ 0.41 ± 0.06; PBS 0.57 ± 0.03, p < 0.005) At Day 3 and 5, there was no significant difference in Has2 and Has3 levels in AdIl-10 treated wounds vs. controls. Conclusions. Adenoviral mediated overexpression of Il-10 results in the differential expression of Has1 at day 3 and 5. Has1 encodes for high molecular weight HA, which is associated with inhibition of angiogenesis and leukocyte infiltrates as observed in the HA-rich environment of fetal wounds. The effects of AdIl-10 may in part be due to the differential expression of Has1 creating a permissive environment for fetal-like scarless wound repair.