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, Ju Hee Lee, Chae Ok Yun

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21 Citations (Scopus)


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
Issue number1
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2014051295, W.J. Lee).

Publisher Copyright:
© 2018 The Author(s).

All Science Journal Classification (ASJC) codes

  • General


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