Calreticulin promotes angiogenesis via activating nitric oxide signalling pathway in rheumatoid arthritis

被引:35
作者
Ding, H. [1 ,3 ]
Hong, C. [1 ]
Wang, Y. [4 ]
Liu, J. [3 ]
Zhang, N. [2 ]
Shen, C. [1 ]
Wei, W. [2 ]
Zheng, F. [1 ]
机构
[1] Tianjin Med Univ, Sch Lab Med, Dept Immunol, Gen Hosp, Tianjin 300203, Peoples R China
[2] Tianjin Med Univ, Dept Rheumatol, Gen Hosp, Tianjin 300203, Peoples R China
[3] Second Hosp Tangshan, Tangshan, Peoples R China
[4] Chest Hosp Xian, Dept Lab Med, Xian, Peoples R China
关键词
angiogenesis; calreticulin; nitric oxide; rheumatoid arthritis; ENDOTHELIAL GROWTH-FACTOR; CHRONIC INFLAMMATION; SHARED EPITOPE; IMMUNE-SYSTEM; IN-VIVO; DISEASE; PATHOGENESIS; CELLS; APOPTOSIS; PANNUS;
D O I
10.1111/cei.12411
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Calreticulin (CRT) is a multi-functional endoplasmic reticulum protein implicated in the pathogenesis of rheumatoid arthritis (RA). The present study was undertaken to determine whether CRT was involved in angiogenesis via the activating nitric oxide (NO) signalling pathway. We explored the profile of CRT expression in RA (including serum, synovial fluid and synovial tissue). In order to investigate the role of CRT on angiogenesis, human umbilical vein endothelial cells (HUVECs) were isolated and cultured in this study for in-vitro experiments. Our results showed a significantly higher concentration of CRT in serum (5.4 +/- 2.2 ng/ml) of RA patients compared to that of osteoarthritis (OA, 3.6 +/- 0.9 ng/ml, P < 0.05) and healthy controls (HC, 3.7 +/- 0.6 ng/ml, P < 0.05); and significantly higher CRT in synovial fluid (5.8 +/- 1.2 ng/ml) of RA versus OA (3.7 +/- 0.3 ng/ml, P < 0.05). High levels of CRT are expressed in synovial membrane localized predominantly to inflammatory cells and synovial perivascular areas in both the lining and sublining layers of RA synovial tissue (RAST). Increased nitric oxide (NO) production and phosphorylation level of endothelial nitric oxide synthase (eNOS) were measured in HUVECs following CRT stimulation, while the total eNOS expression was not significantly changed. Furthermore, CRT promoted the proliferation, migration and tube formation of HUVECs, which were significantly inhibited by a specific eNOS inhibitor. These findings suggested that CRT may be involved in angiogenesis events in RA through NO signalling pathways, which may provide a potential therapeutic target in the treatment of RA.
引用
收藏
页码:236 / 244
页数:9
相关论文
共 43 条
[1]   THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].
ARNETT, FC ;
EDWORTHY, SM ;
BLOCH, DA ;
MCSHANE, DJ ;
FRIES, JF ;
COOPER, NS ;
HEALEY, LA ;
KAPLAN, SR ;
LIANG, MH ;
LUTHRA, HS ;
MEDSGER, TA ;
MITCHELL, DM ;
NEUSTADT, DH ;
PINALS, RS ;
SCHALLER, JG ;
SHARP, JT ;
WILDER, RL ;
HUNDER, GG .
ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324
[2]   Nitric oxide and the immune response [J].
Bogdan, C .
NATURE IMMUNOLOGY, 2001, 2 (10) :907-916
[3]   Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47 [J].
Chao, Mark P. ;
Jaiswal, Siddhartha ;
Weissman-Tsukamoto, Rachel ;
Alizadeh, Ash A. ;
Gentles, Andrew J. ;
Volkmer, Jens ;
Weiskopf, Kipp ;
Willingham, Stephen B. ;
Raveh, Tal ;
Park, Christopher Y. ;
Majeti, Ravindra ;
Weissman, Irving L. .
SCIENCE TRANSLATIONAL MEDICINE, 2010, 2 (63)
[4]   Life history of eNOS: Partners and pathways [J].
Dudzinski, David M. ;
Michel, Thomas .
CARDIOVASCULAR RESEARCH, 2007, 75 (02) :247-260
[5]  
HAMILTON JA, 1983, J RHEUMATOL, V10, P845
[6]   A role for calreticulin in the pathogenesis of rheumatoid arthritis [J].
Holoshitz, Joseph ;
De Almeida, Denise E. ;
Ling, Song .
CLEARANCE OF DYING CELLS IN HEALTHY AND DISEASED IMMUNE SYSTEMS, 2010, 1209 :91-98
[7]   Functional Analysis of Recombinant Calreticulin Fragment 39-272: Implications for Immunobiological Activities of Calreticulin in Health and Disease [J].
Hong, Chao ;
Qiu, Xiang ;
Li, Yue ;
Huang, Qianrong ;
Zhong, Zhaoyan ;
Zhang, Yan ;
Liu, Xiangyuan ;
Sun, Lin ;
Lv, Ping ;
Gao, Xiao-Ming .
JOURNAL OF IMMUNOLOGY, 2010, 185 (08) :4561-4569
[8]   The ins and outs of calreticulin: from the ER lumen to the extracellular space [J].
Johnson, S ;
Michalak, M ;
Opas, M ;
Eggleton, P .
TRENDS IN CELL BIOLOGY, 2001, 11 (03) :122-129
[9]   Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes [J].
Kim, MS ;
Kwon, HJ ;
Lee, YM ;
Baek, JH ;
Jang, JE ;
Lee, SW ;
Moon, EJ ;
Kim, HS ;
Lee, SK ;
Chung, HY ;
Kim, CW ;
Kim, KW .
NATURE MEDICINE, 2001, 7 (04) :437-443
[10]  
Koch AE, 1998, ARTHRITIS RHEUM-US, V41, P951, DOI 10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO