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작성일 : 18-08-28 13:27
Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis.
국내/국외 구분: 국외
SCI/SCIE/비SCI 구분: SCI
논문제목: Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis.
제 1저자, 교신저자:
나머지 저자: Lee CJ, Moon SJ, Jeong JH, Lee S, Lee MH, Yoo SM, Lee HS, Kang HC, Lee JY, Lee WS, Lee HJ, Kim EK, Jhun JY, Cho ML, Min JK, Cho YY.
학술지명: Cell Death & Disease
Vol(No),페이지:
발행년월일: 2018/03/01
v파일다운로드: 2018/03/01

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3-RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68+ macrophages with high frequency, while pRSK2-expressing CD4+ T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3-RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.


 
 

 
Total 176
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, Park JS, Kim NR, Lim MA, Kim SM, Hwang SH, Jung KA, Choi J, Park SH, Cho ML.
Deficiency of IL-1 receptor antagonist suppresses IL-10-producing B cells in autoimmune arthritis in an IL-17/Th17-dependent manner To be published in: Immunology Letters
Immunology Letters, 2018/07,
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, Lee SH, Lee HR, Kwon JY, Jung K, Kim SY, Cho KH, Choi J, Lee HH, Lee BI, Jue DM, Cho ML.
A20 ameliorates inflammatory bowel disease in mice via inhibiting NF-κB and STAT3 activation.
Immunology Letters, 2018/06,
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, Jhun J, Lee SH, Lee SK, Kim HY, Jung ES, Kim DG, Choi J, Bae SH, Yoon SK, Chung BH, Yang CW, Cho ML, Choi JY.
Serial Monitoring of Immune Markers Being Represented Treg/Th17 Ratio: Indicating Tolerance for Tapering Immunosuppression after Liver Transplantation
Front Immunol., 2018/03,
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, Kwon JE, Lee SY, Seo HB, Moon YM, Ryu JG, Jung KA, Jhun JY, Park JS, Hwang SS, Kim JM, Lee GR, Park SH, Cho ML.
YinYang1 deficiency ameliorates joint inflammation in a murine model of rheumatoid arthritis by modulating Th17 cell activation.
Immunology Letters, 2018/05,
국외
, Lee CJ, Moon SJ, Jeong JH, Lee S, Lee MH, Yoo SM, Lee HS, Kang HC, Lee JY, Lee WS, Lee HJ, Kim EK, Jhun JY, Cho ML, Min JK, Cho YY.
Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis.
Cell Death & Disease, 2018/03/01,
국외
, Jung SM, Lee J, Baek SY, Lee J, Jang SG, Hong SM, Park JS, Cho ML, Park SH, Kwok SK.
Fraxinellone Attenuates Rheumatoid Inflammation in Mice.
International journal of molecular sciences, 2018/03/13,
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, Park MJ, Lee SH, Kim EK, Lee EJ, Baek JA, Park SH, Kwok SK, Cho ML.
Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice
Scientific Reports, 2018/02/01,
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, Park JS, Choi J, Kwon JY, Jung KA, Yang CW, Park SH, Cho ML.
A Probiotic Complex, Rosavin, Zinc, and Prebiotics Ameliorate Intestinal Inflammation in an Acute Colitis Mouse Model
"Journal of Translational Medicine, 2018/02/21,
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, Kim EK, Lee SH, Lee SY, Kim JK, Jhun JY, Na HS, Kim SY, Choi JY, Yang CW, Park SH, Cho ML.
Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation.
Experimental & Molecular Medicine, 2018/01/26,
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, Lee SY, Lee SH, Jhun J, Seo HB, Jung KA, Yang CW, Park SH, Cho ML.
A Combination with Probiotic Complex, Zinc, and Coenzyme Q10 Attenuates Autoimmune Arthritis by Regulation of Th17/Treg Balance.e
Journal of Medicinal Food, 2018/01,
국외
, Kwon JY, Lee SH, Jhun J, Choi J, Jung K, Cho KH, Kim SJ, Yang CW, Park SH, Cho ML.
"The combination of probiotic complex, rosavin and zinc improves pain and cartilage destruction an in osteoarthritis rat model Short title: Probiotic complex, rosavin and zinc alleviates OA
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, Park JS, Choi J, Jhun J, Kwon JY, Lee BI, Yang CW, Park SH, Cho ML.
Lactobacillus acidophilus Improves Intestinal Inflammation in an Acute Colitis Mouse Model by Regulation of Th17 and Treg Cell Balance and Fibrosis Development.
Journal of Medicinal Food, 2018/03/01,
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, Moon YM, Lee SY, Kwok SK, Lee SH, Kim D, Kim WK, Her YM, Son HJ, Kim EK, Ryu JG, Seo HB, Kwon JE, Hwang SY, Youn J, Seong RH, Jue DM, Park SH, Kim HY, Ahn SM, Cho ML.
The Fos-Related Antigen 1– JUNB/ Activator Protein 1 Transcription Complex, a Downstream Target of Signal Transducer and Activator of Transcription 3, Induces T Helper 17 Differentiation and Promotes Experimental Autoimmune Arthritis
Front Immunol., 2017/12/18,
국외
, Jung SM, Lee J, Baek SY, Lee J, Jang SG, Hong SM, Park JS, Cho ML, Park SH, Kwok SK.
Ethyl pyruvate ameliorates inflammatory arthritis in mice.
International Immunopharmacology, 2017/11,
국외
, Lee SH, Kwon JY, Kim SY, Jung K, Cho ML.
INTERFERON-GAMMA REGULATES INFLAMMATORY CELL DEATH BY TARGETING NECROPTOSIS IN EXPERIMENTAL AUTOIMMUNE ARTHRITIS
Scientific Reports, 2017/08,
 
 
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