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

Title
Profibrogenic effect of high-mobility group box protein-1 in human dermal fibroblasts and its excess in keloid tissues
Author
윤채옥
Keywords
COLLAGEN-SYNTHESIS; MESENCHYMAL TRANSITION; STERILE INFLAMMATION; EMERGING ROLE; 1 HMGB1; PATHOGENESIS; DISEASE; INHIBITION; ACTIVATION; EXPRESSION
Issue Date
2018-05
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v. 8, Article no. 8434
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-beta 1 and internal signaling molecules, such as Smad 2 and 3, phosphorylated Smad 2/3 complex, Erk 1/2, Akt, and NF-kappa B. 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.
URI
https://www.nature.com/articles/s41598-018-26501-6http://repository.hanyang.ac.kr/handle/20.500.11754/118552
ISSN
2045-2322
DOI
10.1038/s41598-018-26501-6
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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