Andrea Hoffmann1, Jessica Lynn Hoing2, Mackenzie Newman2, Richard Simman1. 1. Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA ; Department of Surgery, Division of Plastic Surgery, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA. 2. Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.
Abstract
BACKGROUND: Keloids are benign dermal scars characterized by enhanced growth factor signaling, hyperproliferation activity and reduced extracellular matrix (ECM) deposition of hyaluronic acid. Our hypothesis is that high molecular weight HA can be used to replenish HA deposition in keloids thereby normalizing the keloid fibroblast phenotype. METHODS: One normal (NF1) fibroblast culture and five keloid (KF1, KF2, KF3, KF4, KF5) fibroblast cultures were analyzed for changes in hyperproliferation, growth factor production and extracellular matrix deposition following 72 hour treatment with or without 10 μg/ml HA. RESULTS: Proliferation activity decreased significantly in KF3 following HA treatment. Pro-collagen I expression in KF2 was decreased following HA treatment in association with changes in fiber arrangement to more parallel collagen bundles. In addition, HA demonstrated a downregulation on TGF-b1 growth factor expression in KF3 and KF4 and a decrease in active TGF-b1 release in KF2 and KF5 using ELISA. CONCLUSION: Our data demonstrates that HA has the potential to normalize keloid fibroblast characteristic features such as hyperproliferation, growth factor production and ECM deposition depending on the specific genotype of the keloid fibroblast cell line. This study suggests that high molecular weight HA can be used to replenish HA deposition in keloid fibroblasts thereby decreasing fibrosis and ultimately decreasing keloid manifestation.
BACKGROUND: Keloids are benign dermal scars characterized by enhanced growth factor signaling, hyperproliferation activity and reduced extracellular matrix (ECM) deposition of hyaluronic acid. Our hypothesis is that high molecular weight HA can be used to replenish HA deposition in keloids thereby normalizing the keloid fibroblast phenotype. METHODS: One normal (NF1) fibroblast culture and five keloid (KF1, KF2, KF3, KF4, KF5) fibroblast cultures were analyzed for changes in hyperproliferation, growth factor production and extracellular matrix deposition following 72 hour treatment with or without 10 μg/ml HA. RESULTS: Proliferation activity decreased significantly in KF3 following HA treatment. Pro-collagen I expression in KF2 was decreased following HA treatment in association with changes in fiber arrangement to more parallel collagen bundles. In addition, HA demonstrated a downregulation on TGF-b1 growth factor expression in KF3 and KF4 and a decrease in active TGF-b1 release in KF2 and KF5 using ELISA. CONCLUSION: Our data demonstrates that HA has the potential to normalize keloid fibroblast characteristic features such as hyperproliferation, growth factor production and ECM deposition depending on the specific genotype of the keloid fibroblast cell line. This study suggests that high molecular weight HA can be used to replenish HA deposition in keloid fibroblasts thereby decreasing fibrosis and ultimately decreasing keloid manifestation.
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