PMID- 25692286
OWN - NLM
STAT- MEDLINE
DCOM- 20151111
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 2
DP  - 2015
TI  - High mobility group box 1 induced human lung myofibroblasts differentiation and 
      enhanced migration by activation of MMP-9.
PG  - e0116393
LID - 10.1371/journal.pone.0116393 [doi]
LID - e0116393
AB  - High mobility group box 1 (HMGB1) is a nuclear protein that involves the binding 
      with DNA and influences chromatin regulation and transcription. HMGB1 is also a 
      cytokine that can activate monocytes and neutrophils involved in inflammation. In 
      this study, we investigated the role of HMGB1 on cellular activation using human 
      fibroblast cell line WI-38. After treatment with 1, 10, and 100 ng/mL of HMGB1 
      for 24 h, we did not find obviously cytotoxicity and cellular proliferation of 
      WI-38 cells by MTT and BrdU incorporation assay, respectively. However, we found 
      that treatment with 10 and 100 ng/mL of HMGB1 induced the differentiation of lung 
      fibroblasts into myofibroblasts and myofibroblasts showed higher migration 
      ability through activation of matrix metalloproteinase (MMP)-9 activation. To 
      delineate the mechanism underlying HMGB1-induced cellular migration, we examined 
      HMGB1-induced mitogen activated protein kinases (MAPKs), including extracellular 
      signal related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen 
      activated protein kinase (p38) phosphorylation, as well as nuclear factor (NF)-kappaB 
      nuclear translocation. Using specific inhibitors and shRNAs of protein kinases, 
      we observed that repression of ERK, JNK, p38, and NF-kappaB all inhibited 
      HMGB1-induced cellular differentiation, migration and MMP-9 activation in WI-38 
      cells. In addition, knocking down of RAGE but not TLR2 and TLR4 by shRNAs 
      attenuated HMGB1-induced myofibroblast differentiation and migration. In 
      conclusion, our study demonstrated that HMGB1 induced lung fibroblasts' 
      differentiation into myofibroblasts and enhanced cell migration through induction 
      of MMP-9 activation and the RAGE-MAPK and NF-kappaB interaction signaling pathways. 
      Targeting HMGB1 might be a potential therapeutic approach for alleviation of 
      airway remodeling seen in chronic airway inflammatory diseases.
FAU - Lee, Chen-Chen
AU  - Lee CC
AD  - Department of Microbiology and Immunology, School of Medicine, China Medical 
      University, Taichung, Taiwan; Graduate Institute of Basic Medical Science, 
      College of Medicine, China Medical University, Taichung, Taiwan.
FAU - Wang, Chien-Neng
AU  - Wang CN
AD  - Graduate Institute of Basic Medical Science, College of Medicine, China Medical 
      University, Taichung, Taiwan.
FAU - Lee, Yueh-Lun
AU  - Lee YL
AD  - Department of Microbiology and Immunology, School of Medicine, College of 
      Medicine, Taipei Medical University, Taipei, Taiwan.
FAU - Tsai, Yi-Ru
AU  - Tsai YR
AD  - Graduate Institute of Basic Medical Science, College of Medicine, China Medical 
      University, Taichung, Taiwan.
FAU - Liu, Jau-Jin
AU  - Liu JJ
AD  - Department of Microbiology and Immunology, School of Medicine, China Medical 
      University, Taichung, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150218
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HMGB1 Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Cell Movement/*drug effects
MH  - Enzyme Activation/drug effects
MH  - Fibroblasts/cytology
MH  - HMGB1 Protein/*pharmacology
MH  - Humans
MH  - Lung/*cytology
MH  - MAP Kinase Signaling System/drug effects
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Myofibroblasts/*cytology/*drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/metabolism
PMC - PMC4332862
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/02/19 06:00
MHDA- 2015/11/12 06:00
PMCR- 2015/02/18
CRDT- 2015/02/19 06:00
PHST- 2014/05/02 00:00 [received]
PHST- 2014/12/10 00:00 [accepted]
PHST- 2015/02/19 06:00 [entrez]
PHST- 2015/02/19 06:00 [pubmed]
PHST- 2015/11/12 06:00 [medline]
PHST- 2015/02/18 00:00 [pmc-release]
AID - PONE-D-14-19784 [pii]
AID - 10.1371/journal.pone.0116393 [doi]
PST - epublish
SO  - PLoS One. 2015 Feb 18;10(2):e0116393. doi: 10.1371/journal.pone.0116393. 
      eCollection 2015.