更新于：2024-11-01

TRAIL x TNFRSF11B x RANK

更新于：2024-11-01

基本信息

关联

项与 TRAIL x TNFRSF11B x RANK 相关的药物

KY-3

靶点

RANK x TNFRSF11B x TRAIL

作用机制

RANK抑制剂 [+2]

在研机构

Kymab Ltd. [+1]

原研机构

The University of Sheffield

在研适应症

肺动脉高压

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRAIL x TNFRSF11B x RANK 相关的临床结果

登录后查看更多信息

100 项与 TRAIL x TNFRSF11B x RANK 相关的转化医学

登录后查看更多信息

0 项与 TRAIL x TNFRSF11B x RANK 相关的专利（医药）

登录后查看更多信息

项与 TRAIL x TNFRSF11B x RANK 相关的文献（医药）

2022-07-01·Heart Failure Reviews2区 · 医学

Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases

2区 · 医学

Review

作者: Wojakowski, Wojciech ; Zimmer, Karolina ; Dutka, Mieczysław ; Francuz, Tomasz ; Pająk, Celina ; Bobiński, Rafał

AbstractOsteoprotegerin (OPG) is a glycoprotein involved in the regulation of bone remodelling. OPG regulates osteoclast activity by blocking the interaction between the receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL). More and more studies confirm the relationship between OPG and cardiovascular diseases. Numerous studies have confirmed that a high plasma concentration of OPG and a low concentration of tumour necrosis factor–related apoptosis inducing ligand (TRAIL) together with a high OPG/TRAIL ratio are predictors of poor prognosis in patients with myocardial infarction. A high plasma OPG concentration and a high ratio of OPG/TRAIL in the acute myocardial infarction are a prognostic indicator of adverse left ventricular remodelling and of the development of heart failure. Ever more data indicates the participation of OPG in the regulation of the function of vascular endothelial cells and the initiation of the atherosclerotic process in the arteries. Additionally, it has been shown that TRAIL has a protective effect on blood vessels and exerts an anti-atherosclerotic effect. The mechanisms of action of both OPG and TRAIL within the cells of the vascular wall are complex and remain largely unclear. However, these mechanisms of action as well as their interaction in the local vascular environment are of great interest to researchers. This article presents the current state of knowledge on the mechanisms of action of OPG and TRAIL in the circulatory system and their role in cardiovascular diseases. Understanding these mechanisms may allow their use as a therapeutic target in cardiovascular diseases in the future.

2020-02-01·Clinical & Experimental Metastasis3区 · 医学

Harnessing the versatile role of OPG in bone oncology: counterbalancing RANKL and TRAIL signaling and beyond

3区 · 医学

Review

作者: Deligiorgi, Maria V ; Griniatsos, John ; Panayiotidis, Mihalis I ; Trafalis, Dimitrios T

More than 2 decades ago, the discovery of osteoprotegerin (OPG) as inhibitor of the receptor of activator of nuclear factor Kb (RANK) ligand (RANKL) revolutionized our understanding of bone biology and oncology. Besides acting as decoy receptor for RANKL, OPG acts as decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). OPG, RANKL, and TRAIL are ubiquitously expressed, stimulating per se pivotal signaling cascades implicated in cancer. In the context of cancer cell-bone cell interactions, cancer cells skew the OPG/RANKL/RANK (RANKL cognate receptor) balance towards bone destruction and tumor growth through favoring the RANKL/RANK interface, circumventing OPG. Numerous preclinical and clinical studies demonstrate the dual role of OPG in cancer: antitumor and tumor-promoting. OPG potentially conveys an antitumor signal through inhibiting the tumor-promoting RANKL signaling-both the osteoclast-dependent and the osteoclast-independent-and the tumor-promoting TRAIL signaling. On the other hand, the presumed tumor-promoting functions of OPG are: (i) abrogation of TRAIL-induced apoptosis of cancer cells; (ii) abrogation of RANKL-induced antitumor immunity; and (iii) stimulation of oncogenic and prometastatic signaling cascades downstream of the interaction of OPG with diverse proteins. The present review dissects the role of OPG in bone oncology. It presents the available preclinical and clinical data sustaining the dual role of OPG in cancer and focuses on the imbalanced RANKL/RANK/OPG interplay in the landmark "vicious cycle" of skeletal metastatic disease, osteosarcoma, and multiple myeloma. Finally, current challenges and future perspectives in exploiting OPG signaling in bone oncology therapeutics are discussed.

2020-01-01·The Journal of Immunology

IL-17 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas

Article

作者: Gao, Nan ; Me, Rao ; Yu, Fu-shin X. ; Dai, Chenyang

AbstractThe aim of this study was to elucidate the expression and functions of IL-17 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. We found that P. aeruginosa infection induced and increased signaling of IL-23/23R/17/17R in mouse corneas. Targeting IL-17A or the IL-17A–specific receptor IL-17RA/IL-17RC with neutralizing Abs resulted in a significant decrease in the severity of P. aeruginosa keratitis, including a decrease in bacterial burden and polymorphonuclear leukocyte infiltration. IL-17A–signaling blockade also significantly reduced the expression of the proinflammatory cytokines L-1β, IL-24, and MMP-13 and increased the expression of the anti-inflammatory cytokine IL-1RA in mouse corneal epithelium. The presence of mouse IL-17A exacerbated P. aeruginosa–mediated tissue destruction. A cytokine protein array revealed that the expression of osteoprotegerin (OPG) was regulated by IL-17A, and OPG neutralization also resulted in a decrease in the severity of P. aeruginosa keratitis. Although both IL-17 and OPG affected the balanced expression of IL-1β and IL-1RA, only IL-17 inhibited the expression of TH2 cytokines. Taken together, our results revealed that IL-17A, along with its downstream factor OPG, plays a detrimental role in the pathogenesis of P. aeruginosa keratitis. Targeting IL-17A and/or the OPG/RANKL/RANK/TRAIL system is a potential therapeutic strategy in controlling the outcome of P. aeruginosa keratitis, which was demonstrated by concurrent topical application of IL-17A–neutralizing Ab and ciprofloxacin in B6 mice.