Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-κB, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-β, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-β-treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.
Bibliographical noteFunding Information:
Funding: This research was funded by a faculty research grant of Yonsei University College of Medicine for 2014 (6-2013-0164).
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry