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High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-kappaB Signaling in Keloid Scar Formation

 Jihee Kim  ;  Jong-Chul Park  ;  Mi Hee Lee  ;  Chae Eun Yang  ;  Ju Hee Lee  ;  Won Jai Lee 
 International Journal of Molecular Sciences, Vol.19(1) : 76, 2018 
Journal Title
 International Journal of Molecular Sciences 
Issue Date
HMGB1 ; fibroblast ; hypertrophic scar ; keloid
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-kappaB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-kappaB 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-beta. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)-mitogen-activated protein kinases (MAPK) and NF-kappaB 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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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
Yonsei Authors
김지희(Kim, Jihee) ORCID logo https://orcid.org/0000-0002-0047-5941
박종철(Park, Jong Chul) ORCID logo https://orcid.org/0000-0003-0083-5991
양채은(Yang, Chae Eun) ORCID logo https://orcid.org/0000-0001-8128-791X
이미희(Lee, Mi Hee) ORCID logo https://orcid.org/0000-0002-9630-7044
이원재(Lee, Won Jai) ORCID logo https://orcid.org/0000-0003-3056-0503
이주희(Lee, Ju Hee) ORCID logo https://orcid.org/0000-0002-1739-5956
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