2014 MRC성과발표회
Abstract Information
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< Abstract Sample >
Hypoxia-inducible factor (HIF)-2 is an Essential Catabolic Regulator of
Inflammatory Rheumatoid Arthritis
Je-Hwang, Ryu
School of Dentistry, Chonnam National University, Republic of Korea
Rheumatoid arthritis (RA) is a systemic autoimmune disorder that manifests as chronic inflammation
and joint tissue destruction. However, the etiology and pathogenesis of RA have not been fully
elucidated. Here, we explored the role of the hypoxia-inducible factors (HIFs), HIF-1 (encoded by
HIF1A) and HIF-2 (encoded by EPAS1). HIF-2 was markedly up-regulated in the intimal lining of
RA synovium, whereas HIF-1 was detected in a few cells in the sublining and deep layer of RA
synovium. Overexpression of HIF-2 in joint tissues caused a RA-like phenotype, whereas HIF-1
did not affect joint architecture. Moreover, a HIF-2 deficiency in mice blunted the development of
experimental RA. HIF-2 was expressed mainly in fibroblast-like synoviocytes (FLS) of RA
synovium and regulated their proliferation, expression of RANKL (receptor activator of nuclear
factor-B ligand) and various catabolic factors, and osteoclastogenic potential. Moreover, HIF-2dependent up-regulation of interleukin (IL)-6 in FLS stimulated differentiation of TH17 cells—crucial
effectors of RA pathogenesis. Additionally, in the absence of IL-6 (Il6/ mice), overexpression of
HIF-2 in joint tissues did not cause a RA phenotype. Thus, our results collectively suggest that HIF2 plays a pivotal role in the pathogenesis of RA by regulating FLS functions, independent of HIF-1.
References
[1] Ryu JH, Chae CS, Kwak JS, Oh H, Shin Y, Huh YH, Lee CG, Park YW, Chun CH, Kim YM, Im
SH, Chun JS. Hypoxia-inducible factor-2α is an essential catabolic regulator of inflammatory
rheumatoid arthritis. PLoS Biol. 2014 Jun 10;12(6).
[2] Ryu JH, Yang S, Shin Y, Rhee J, Chun CH, Chun JS. Interleukin-6 plays an essential role in
hypoxia-inducible factor 2α-induced experimental osteoarthritic cartilage destruction in mice.
Arthritis Rheum. 2011 Sep;63(9):2732-43.
[3] Yang S, Kim J, Ryu JH, Oh H, Chun CH, Kim BJ, Min BH, Chun JS. Hypoxia-inducible factor2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med. 2010 Jun;16(6):687-93.
Keywords: Arthritis, Synoviocyte, Hypoxia-inducible factor (HIF)
2014
MRC 성과발표회
Name : Je-Hwang Ryu
Affiliation : Department of Pharmacology and Dental Therapeutics
School of Dentistry, Chonnam National University
Position : Assistant Professor
E-mail : jesryu@jnu.ac.kr
Field of Expertise : Osteoarthritis, Rheumatoid arthritis, Osteoporosis
Education :
2002. 03 –2006. 08: PhD, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea
2000. 09 –2002. 02: MS, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea
1994. 03 –1999. 02: BS, Chonnam National University, Gwangju, Korea
Professional Experience :
2006. 09 –2008. 08: Post-Doc, Columbia University Medical School, New York, USA
2008. 09–2012. 07: Research Professor, Gwangju Institute of Science and Technology (GIST),
Gwangju, Korea
2012. 08–Present: Assistant Professor in Department of Pharmacology and Dental Therapeutics,
School of Dentistry, Chonnam National University, Gwangju, Korea
Selected Publications :
1. Hypoxia-inducible factor-2α is an essential catabolic regulator of inflammatory rheumatoid
arthritis. Ryu JH, Chae CS, Kwak JS, Oh H, Shin Y, Huh YH, Lee CG, Park YW, Chun CH, Kim
YM, Im SH, Chun JS. PLoS Biol. 2014 Jun 10;12(6).
2. Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis. Kim JH, Jeon J,
Shin M, Won Y, Lee M, Kwak JS, Lee G, Rhee J, Ryu JH, Chun CH, Chun JS. Cell. 2014 Feb
13;156(4):730-43.
3. Low-density lipoprotein receptor-related protein 5 governs Wnt-mediated osteoarthritic cartilage
destruction. Shin Y, Huh YH, Kim K, Kim S, Park KH, Koh JT, Chun JS, Ryu JH Arthritis Res
Ther. 2014 Jan 31;16(1).
4. NAMPT (visfatin), a direct target of hypoxia-inducible factor-2α, is an essential catabolic
regulator of osteoarthritis. Yang S*, Ryu JH*, Oh H, Jeon J, Kwak JS, Kim JH, Kim HA, Chun
CH, Chun JS. Ann Rheum Dis. 2013 Dec 17. doi: 10.1136 *co-first author
5. Hypoxia-inducible factor-2α regulates Fas-mediated chondrocyte apoptosis during osteoarthritic
cartilage destruction. Ryu JH, Shin Y, Huh YH, Yang S, Chun CH, Chun JS. Cell Death Differ.
2012 Mar;19(3):440-50.