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

Jihee Kim, Jongchul Park, Mi Hee Lee, Chae Eun Yang, JuHee Lee, Won Jai Lee

Research output: Contribution to journalArticle

6 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 1

Fingerprint

Keloid
Proto-Oncogene Proteins c-akt
scars
fibroblasts
Fibroblasts
Mitogen-Activated Protein Kinases
Cicatrix
boxes
proteins
Proteins
Glycyrrhizic Acid
products
Skin
Mitogen-Activated Protein Kinase 3
Acids
Mitogen-Activated Protein Kinase 1
Wound Healing
Assays
wound healing
Fibrosis

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "High-mobility group box 1 mediates fibroblast activity via RAGE-MAPK and NF-κB signaling in keloid scar formation",
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.",
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High-mobility group box 1 mediates fibroblast activity via RAGE-MAPK and NF-κB signaling in keloid scar formation. / Kim, Jihee; Park, Jongchul; Lee, Mi Hee; Yang, Chae Eun; Lee, JuHee; Lee, Won Jai.

In: International journal of molecular sciences, Vol. 19, No. 1, 76, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Park, Jongchul

AU - Lee, Mi Hee

AU - Yang, Chae Eun

AU - Lee, JuHee

AU - Lee, Won Jai

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AB - 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.

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