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Fn14
Future Science OA · 2025 · IF 2.1

TWEAK/Fn14 axis may promote vascular smooth muscle cell senescence via p38 signaling pathway: preliminary evidence

Chunyang Wei,Xiaoying Liu,Zhuang Miao,Hua Zhang,Yanfu Wang,Guoxian Qi

Aim The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.Methods Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated. Additionally, the role of p38 phosphorylation pathway in the effect of TWEAK on VSMCs senescence was assessed.Results Expressions of TWEAK and Fn14 were significantly elevated in senescent VSMCs. TWEAK activated the p38 phosphorylation pathway and promoted the SA-β-gal staining and P53 expression.Conclusion These preliminary findings suggest that the TWEAK/Fn14 axis may play a crucial role in promoting VSMC senescence.

CAS / MDL: 4474-91-3
研究领域: 心血管研究 · 细胞信号传导 · 分子生物学
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ANALYTICAL BIOCHEMISTRY · 2019 · IF 2.507

A single molecule assay for ultrasensitive detection of Fn14 in human serum

Yichen Chen,Qiyong Cai,Song Liu

Fibroblast growth factor inducible-14 (Fn14) is a receptor protein that plays an important role in the progression of cancer and some other diseases. Here, an ultrasensitive assay was developed for the detection of Fn14 based on a digital sandwich enzyme-linked immunosorbent bead-based assay (dELISA). Beads containing a single immunocomplex are loaded into microwells (~46 fL) and produce fluorescence through enzyme-catalyzed reactions in extremely small volumes. By measuring the number of fluorescent microwells in arrays arranged on a circular Disc, the concentration of Fn14 was determined. To obtain better performance for Fn14 detection, assay conditions including reagent concentrations and measurement parameters were optimized and 44 different antibody pairs were screened. The detection range of Fn14 is 1.26 pg/mL to 3683 pg/mL with a lower detection limit of 0.32 pg/mL, which is much lower than that of conventional ELISAs . In addition, the total operation of this assay is automated and only takes approximately an hour to accomplish. Furthermore, this assay was successfully applied to the determination of spiked Fn14 in serum samples with satisfactory performance.

CAS / MDL: 9005-64-5
研究领域: 生物标志物检测 · 癌症研究 · 分子生物学 · 分析化学
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Donor Substitution Engineering of Hemicyanine Nanoparticles to Reprogram the Tumor Microenvironment and Enhance Fn14-Targeted BiTE for Glioblastoma Photoimmunotherapy

Gaowei Li,Shichao Jiang,Zongliang Zhang,Xiaoyin Liu,Kai Wu,Peng Liu,Mei Yang,Ting Zhou,Jiamei Xiao,Nini Xin,Xiaoyang Wu,Zhihong Chen,Jie Ding,Chengheng Wu,Dan Wei,Jing Sun,Aiping Tong,Hongsong Fan,Liangxue Zhou

Glioblastoma (GBM) is a highly malignant intracranial tumor with limited treatment options. Bispecific T-cell engagers (BiTEs) are being explored for GBM treatment, but their success is hindered by inadequate T cell infiltration and activation due to the acidic and immunosuppressive microenvironment. Photothermal immunotherapy lyses tumors and activates immune responses, complementing BiTEs. This study innovatively employs a donor engineering strategy to develop hemicyanine dyes (Hcys) that emit from near-infrared (NIR) I to NIR II. The Hcy with excellent properties is encapsulated in an amphiphilic micelle, forming a nano assembly with lactate oxidase (PLH1100). PLH1100 exhibits spectral absorption at 980 nm, a photothermal conversion efficiency of 58.7%, and capability for NIR-II tumor imaging. Besides photothermal tumor ablation, PLH1100 regulates lactic acid metabolism and activates immunogenic cell death, improving the tumor microenvironment and promoting T cell infiltration and activation. Further studies demonstrate PLH1100 effectively kills human and murine GBM cells, inhibits orthotopic U87 tumor growth in BALB/c-nu mice, and enhances the efficacy of Fn14-targeted BiTE in orthotopic GL261 tumors in C57BL/6 mice, achieving a synergistic “1+1>2” therapeutic effect. Collectively, this work opens a new pathway for using Hcy-based molecules combined with BiTE drugs for GBM therapy, with significant clinical potential.

研究领域: 肿瘤学 · 纳米技术 · 免疫疗法 · 分子生物学 · 神经科学
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MEDICAL SCIENCE MONITOR · 2020 · IF 1.918

Quercetin Inhibits the Proliferation and Metastasis of Human Non-Small Cell Lung Cancer Cell Line: The Key Role of Src-Mediated Fibroblast Growth Factor-Inducible 14 (Fn14)/Nuclear Factor kappa B (NF-κB) pathway

Yan Dong,Jun Yang,Liyuan Yang,Ping Li

Background Quercetin (Que) is reported to induce apoptosis of lung cancer cells. Src is closely related to the progression of non-small cell lung cancer (NSCLC) and can be modulated by Que in macrophages. In the current study, the interaction between Que and Src signaling in NSCLC cells was explored to explain the anti-NSCLC function of Que. Material/Methods NSCLC cell line HCC827 was subjected to the administrations of Que at different concentrations. The effect of Que on tumor cell proliferation was detected using MTT and colony formation assays. Then the effect on the migration and invasion abilities was assessed using scratch and Transwell assays. At molecular level, the changes in Src/Fn14/NF-κB signaling were determined using western blotting assays. The role of Src in the function of Que was further explored by inducing the expression of Src gene in NSCLC cells before Que administration. The results of the in vitro assays were verified using a NSCLC mice model. Results Que inhibited the proliferation and anchorage-independent growth of NSCLC cells. Additionally, Que delayed in the gap closure rate in scratch assays and decreased the membrane-penetrating cell number in Transwell assays. At a molecular level, Que suppressed the expression of Src, which subsequently inhibited Fn14/NF-κB signaling. In in vivo assays, Que inhibited the growth of solid tumors. After the overexpression of Src in NSCLC cells, the anti-NSCLC effect of Que was blocked by inducing NSCLC proliferation and metastasis, and by activating Fn14/NF-κB signaling. Moreover, the induced level of Src promoted the growth and metastasis potential of solid tumors in mice. Conclusions Que exerted the anti-NSCLC effect by inhibiting Src-mediated Fn14/NF-κB pathway both in vitro and in vivo .

CAS / MDL: 522-12-3
研究领域: 肿瘤学 · 药理学 · 细胞生物学 · 分子生物学
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