Profibrogenic effect of high-mobility group box protein-1 in human dermal fibroblasts and its excess in keloid tissues

Won Jai Lee, Seung Yong Song, Hyun Roh, Hyo Min Ahn, Youjin Na, Jihee Kim, JuHee Lee, Chae Ok Yun

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

High-mobility group box 1 (HMGB1) protein acts as a DNA chaperone for nuclear homeostasis. It translocates into the cytosol and is secreted into extracellular spaces, triggering proinflammatory cytokines and acting as a mediator in fibrosis. We determined whether HMGB1 plays a role in normal dermal fibrosis and keloid, and is involved with transforming growth factor β. We investigated the translocation and active release of HMGB1 from normal dermal fibroblasts under lipopolysaccharide stimuli, and the redistribution of nuclear HMGB1 into the cytoplasm of keloid fibroblasts. HMGB1 and its effector toll-like receptors and receptors for advanced glycation end product proteins are actively expressed in keloid tissues. Exogenous HMGB1 can induce the proliferation of human dermal fibroblasts, and could act as a profibrogenic molecule to produce collagen, decrease MMP-1, and increase TIMP-1 mRNA expression. Moreover, administration of HMGB1 increased the expression level of TGF-β1 and internal signaling molecules, such as Smad 2 and 3, phosphorylated Smad 2/3 complex, Erk 1/2, Akt, and NF-κB. Collectively, we demonstrate that HMGB1 treatment increases the expression level of collagen types I and III, elastin, and fibronectin in dermal spheroid cultures, thus making HMGB1 a promising therapeutic target for treatment of profibrogenic diseases.

Original languageEnglish
Article number8434
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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HMGB1 Protein
Keloid
Fibroblasts
Skin
Fibrosis
Tissue Inhibitor of Metalloproteinase-1
Collagen Type III
Elastin
Toll-Like Receptors
Extracellular Space
Transforming Growth Factors
Collagen Type I
Matrix Metalloproteinases
Fibronectins
Cytosol
Lipopolysaccharides
Cytoplasm
Homeostasis
Collagen
Cytokines

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Won Jai ; Song, Seung Yong ; Roh, Hyun ; Ahn, Hyo Min ; Na, Youjin ; Kim, Jihee ; Lee, JuHee ; Yun, Chae Ok. / Profibrogenic effect of high-mobility group box protein-1 in human dermal fibroblasts and its excess in keloid tissues. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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Profibrogenic effect of high-mobility group box protein-1 in human dermal fibroblasts and its excess in keloid tissues. / Lee, Won Jai; Song, Seung Yong; Roh, Hyun; Ahn, Hyo Min; Na, Youjin; Kim, Jihee; Lee, JuHee; Yun, Chae Ok.

In: Scientific reports, Vol. 8, No. 1, 8434, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Song, Seung Yong

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AU - Na, Youjin

AU - Kim, Jihee

AU - Lee, JuHee

AU - Yun, Chae Ok

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