High-mobility group box 1 mediates fibroblast activity via RAGE-MAPK and NF-κB signaling in keloid scar formation

Jihee Kim, Jong Chul Park, Mi Hee Lee, Chae Eun Yang, Ju Hee Lee, Won Jai Lee

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)—mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.

Original languageEnglish
Article number76
JournalInternational journal of molecular sciences
Volume19
Issue number1
DOIs
Publication statusPublished - 2018 Jan

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'High-mobility group box 1 mediates fibroblast activity via RAGE-MAPK and NF-κB signaling in keloid scar formation'. Together they form a unique fingerprint.

  • Cite this