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

Authors
 Won Jai Lee  ;  Seung Yong Song  ;  Hyun Roh  ;  Hyo Min Ahn  ;  Youjin Na  ;  Jihee Kim  ;  Ju Hee Lee  ;  Chae Ok Yun 
Citation
 Scientific Reports, Vol.8(1) : 8434, 2018 
Journal Title
 Scientific Reports 
Issue Date
2018
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 beta. 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-beta1 and internal signaling molecules, such as Smad 2 and 3, phosphorylated Smad 2/3 complex, Erk 1/2, Akt, and NF-kappaB. 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.
Files in This Item:
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DOI
10.1038/s41598-018-26501-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jihee(김지희) ORCID logo https://orcid.org/0000-0002-0047-5941
Song, Seung Yong(송승용) ORCID logo https://orcid.org/0000-0002-3145-7463
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162460
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