Last update 01 Nov 2024

TWEAKR

Last update 01 Nov 2024

Basic Info

Synonyms

CD266, FGF-inducible 14, Fibroblast growth factor-inducible immediate-early response protein 14

+ [7]

Introduction

Receptor for TNFSF12/TWEAK. Weak inducer of apoptosis in some cell types. Promotes angiogenesis and the proliferation of endothelial cells. May modulate cellular adhesion to matrix proteins.

Drugs associated with TWEAKR

ASP1531

Target

TWEAKR

Mechanism

TWEAKR antagonists

Active Org.

Astellas Pharma, Inc.

Originator Org.

Astellas Pharma, Inc.

Active Indication

Cachexia [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TSCP-2

Target

TRAIL receptor x TWEAKR

Mechanism

TRAIL receptor modulators [+1]

Active Org.

KAHR Medical Ltd.

Originator Org.

KAHR Medical Ltd.

Active Indication

Rheumatoid Arthritis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WO2022155705

Patent Mining

Target

TWEAKR

Mechanism-

Active Org.

LaTrobe University

Originator Org.

LaTrobe University

Active Indication

Cardiovascular Diseases [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with TWEAKR

NCT00738764 / CompletedPhase 1

A Phase 1, Multicenter, Open-Label, Dose Escalation Trial of PDL192 in Subjects With Advanced Solid Tumors

This is a phase 1, multicenter, open-label, dose escalation trial of PDL192 in subjects with advanced solid tumors.

Start Date01 Jul 2008

Sponsor / Collaborator

Abbott Laboratories

100 Clinical Results associated with TWEAKR

100 Translational Medicine associated with TWEAKR

0 Patents (Medical) associated with TWEAKR

675

Literatures (Medical) associated with TWEAKR

01 Nov 2024·Journal of Orthopaedic Translation

The CD163/TWEAK/Fn14 axis: A potential therapeutic target for alleviating inflammatory bone loss

Article

Author: Wang, Yu-tian ; Cui, Nai-Qian ; Wang, Yu-Tian ; Jiang, Nan ; Liu, Zi-ying ; Cheng, Ning-ning ; Cheng, Ning-Ning ; Liu, Guan-Qiao ; Tian, Liang-jie ; Huang, Kui-yuan ; Deng, Song-Yun ; Yang, Bing-sheng ; Huang, Kui-Yuan ; Xu, Dao-rong ; Xu, Dao-Rong ; Xu, Ya-fei ; Tian, Liang-Jie ; Li, Xiao-ran ; Qian, Ji-kun ; Liu, Guan-qiao ; Ma, Yuan ; Qian, Ji-Kun ; Liu, Zi-Ying ; Yu, Bin ; Li, Xiao-Ran ; Cui, Nai-qian ; Shen, Ke ; Xu, Ya-Fei ; Huang, Xuan ; Yang, Bing-Sheng ; Gu, Yuan ; Chai, Yu ; Deng, Song-yun

ObjectiveOsteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss.MethodsTo assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro.ResultsCD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68⁺ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163.ConclusionOur findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.

01 Oct 2024·iScience

Single-cell RNA sequencing and spatial transcriptomics of bladder Ewing sarcoma

Article

Author: Chen, Ming ; Tao, Tao ; Gu, Chaoming ; Sun, Chao ; Sun, Si ; Xu, Bin ; Wang, Keyi ; Bhattacharya, Atrayee ; Wu, Jianping ; Zhang, Houliang ; Mao, Weipu ; Ji, Jie ; Fang, Cheng ; Geng, Jiang ; Xu, Kangjie ; Chen, Shuqiu

Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.

01 Sep 2024·Cell Stem Cell

Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection

Article

Author: Lu, Tiankun ; Liu, Chengyang ; Parker, Stephen C J ; Parker, Stephen C.J. ; Dong, Xue ; de Silva, Neranjan ; Zhu, Jiajun ; Han, Yuling ; Schwartz, Robert E. ; Wang, Wei ; Robertson, Catherine C ; Zhang, Tuo ; Jeya Vandana, J ; Que, Jianwen ; Yang, Liuliu ; Roy, Aadita ; Chen, Shuibing ; Xiang, Jenny Z. ; Robertson, Catherine C. ; Schwartz, Robert E ; Naji, Ali ; Sun, Yanjie ; Jeya Vandana, J. ; Ge, Jian ; Evans, Todd ; Xiang, Jenny Z ; Pan, Chendong

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of β cell damage during viral exposure.

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TWEAKR

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