更新于：2024-05-01

tenascin

肌腱蛋白

更新于：2024-05-01

基本信息

别名

腱糖蛋白、Cytotactin、deafness, autosomal dominant 56

+ [18]

简介

Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth from cortical neurons grown on a monolayer of astrocytes. Ligand for integrins alpha-8/beta-1, alpha-9/beta-1, alpha-V/beta-3 and alpha-V/beta-6. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (PubMed:19884327).

关联

项与 tenascin 相关的药物

F16 IL2 fusion protein(Philogen SpA)

靶点

IL-2R x tenascin

作用机制

IL-2R激动剂 [+1]

在研机构

Philogen SpA

原研机构

Philogen SpA

在研适应症-

非在研适应症

急性髓性白血病 [+8]

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

Monoclonal antibody F16 I 124(Philogen SpA)

靶点

tenascin

作用机制

tenascin抑制剂 [+1]

在研机构-

原研机构

Philogen SpA

在研适应症-

非在研适应症

肿瘤 [+1]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

Anti-tenascin monoclonal antibody 81C6-I-131

靶点

tenascin

作用机制

tenascin抑制剂 [+1]

在研机构-

原研机构

Duke University Medical Center

在研适应症-

非在研适应症

胶质母细胞瘤 [+1]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 tenascin 相关的临床试验

NCT05468294 / Active, not recruiting临床1/2期

Phase I/IIb Study of the Tumor Targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With the Anti-PD1 Antibody Nivolumab in Patients With Non-small Cell Lung Cancer

Prospective, open label, non-randomized, phase I/IIb study of F16IL2 in combination with Nivolumab.

开始日期2017-03-09

申办/合作机构

Philogen SpA

NCT03207191 / Completed临床1期

A Phase I Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With the Anti-CD33 Antibody BI 836858 in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Phase I, open label, single arm, non-randomized, multicenter, prospective dose escalation study in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT).

开始日期2016-12-02

申办/合作机构

Philogen SpA

[+1]

NCT02957032 / Terminated临床1期

A Dose-finding Phase I Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Very Low-dose Cytarabine in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Phase I, open label, non-randomized, multicenter, prospective dose escalation study of F16IL2 in combination with very low-dose cytarabine in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT).

开始日期2016-04-13

申办/合作机构

Philogen SpA

100 项与 tenascin 相关的临床结果

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100 项与 tenascin 相关的转化医学

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0 项与 tenascin 相关的专利（医药）

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5,495

项与 tenascin 相关的文献（医药）

2024-03-01·International wound journal

Exploring wound management in dental pulp: Utilizing single-cell RNA sequencing for global transcriptomic analysis in healthy and inflamed pulpal tissues.

Article

作者: Nan Gu ; Yao Wang ; Gengtian Sun ; He Zou ; Nan Yang ; Xin Sun ; Zhihui Liu

The process of wound healing in the dental pulp is characterized by intricate interplay of signalling cascades, cellular responses, and extracellular matrix (ECM). The objective of this research was to examine the intricate interaction between signalling cascades, cellular responses, and extracellular matrix (ECM) dynamics that comprise the wound healing process of dental pulp. We conducted a controlled laboratory analysis of transcriptomic landscape of dental pulp tissues, including both healthy and inflamed samples, utilizing single-cell RNA sequencing. We identified significant change in cellular composition under carious conditions by analysing samples from 50 patients. Specifically, the proportion of immune cells increased from 25% to 40%, while the proportion of fibroblasts decreased from 20% to 10%. A transition towards ECM remodelling and fibrosis was indicated by this change. In addition, substantial increase inexpression of critical genes including COL1A1, FN1, IL-1B, IL-6 and TNC was detected, indicating that the extracellular matrix (ECM) was actively remodelled and that a robust inflammatory response was present, both of which are vital for tissue repair. Increased cell-cell interactions among B cells, plasma cells, macrophages and MSCs, and fibroblasts were highlighted in our study, demonstrating the intricate cellular dynamics that occur in response to dental pulp injury. The knowledge gained regarding the cellular and molecular processes underlying pulp wound healing contributed to the advancement of knowledge regarding pulp pathology and regeneration. Moreover, it established a foundation for creation of targeted therapeutic interventions that seek to maximize pulp repair and regeneration. This study represented noteworthy achievement in the field of dental surgery, establishing a solid groundwork for subsequent investigations into regenerative medicine, wound healing, and dental tissue restoration.

2024-02-23·Molecular biology reports

The identification of signature genes and their relationship with immune cell infiltration in age-related macular degeneration.

Article

作者: Jinquan Chen ; Long Zhao ; Longbin Zhang ; Yiling Luo ; Yuling Jiang ; Peng H

BACKGROUND:

Age-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory.

METHOD:

We obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RT‒PCR were used to explore the expression of hub genes in AMD mice.

RESULTS:

We screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-β2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-β2 mRNA and protein in the retinas of AMD mice.

CONCLUSION:

We found that four hub genes, namely, FAP, TGF-β2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.

2024-02-20·Journal of molecular biology

Troponin structural dynamics in the native cardiac thin filament revealed by cryo electron microscopy.

Article

作者: Cristina M Risi ; Betty Belknap ; Jennifer Atherton ; Isabella Leite Coscarella ; Howard D White ; P Bryant Chase ; Jose R Pinto ; Vitold E Galkin

Cardiac muscle contraction occurs due to repetitive interactions between myosin thick and actin thin filaments (TF) regulated by Ca²⁺ levels, active cross-bridges, and cardiac myosin-binding protein C (cMyBP-C). The cardiac TF (cTF) has two nonequivalent strands, each comprised of actin, tropomyosin (Tm), and troponin (Tn). Tn shifts Tm away from myosin-binding sites on actin at elevated Ca²⁺ levels to allow formation of force-producing actomyosin cross-bridges. The Tn complex is comprised of three distinct polypeptides - Ca²⁺-binding TnC, inhibitory TnI, and Tm-binding TnT. The molecular mechanism of their collective action is unresolved due to lack of comprehensive structural information on Tn region of cTF. C1 domain of cMyBP-C activates cTF in the absence of Ca²⁺ to the same extent as rigor myosin. Here we used cryo-EM of native cTFs to show that cTF Tn core adopts multiple structural conformations at high and low Ca²⁺ levels and that the two strands are structurally distinct. At high Ca²⁺ levels, cTF is not entirely activated by Ca²⁺ but exists in either partially or fully activated state. Complete dissociation of TnI C-terminus is required for full activation. In presence of cMyBP-C C1 domain, Tn core adopts a fully activated conformation, even in absence of Ca²⁺. Our data provide a structural description for the requirement of myosin to fully activate cTFs and explain increased affinity of TnC to Ca²⁺ in presence of active cross-bridges. We suggest that allosteric coupling between Tn subunits and Tm is required to control actomyosin interactions.

项与 tenascin 相关的新闻（医药）

2024-04-04

·生物谷

Cell Stem Cell：戴建武/赵燕南团队揭示脊髓发育早期的细胞外基质对神经再生的促进作用

这些结果表明了来自早期发育阶段的细胞外基质（ECM）可能对脊髓的显著再生能力有重要贡献，从而为成人脊髓损伤的治疗带来了新思路。中国科学院遗传与发育生物学研究所戴建武、赵燕南团队（博士生孙政为论文第一作者）在 Cell Stem Cell 期刊发表了题为：Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids 的研究论文。该研究利用多组学技术全面描绘了脊髓细胞外基质（ECM）的发育动态变化，揭示了发育早期的脊髓ECM蛋白在调控脊髓神经干细胞和脊髓类器官再生中发挥重要作用。这些发现促进了我们对神经再生的理解，也为将来开发脊髓损伤（SCI）新疗法提供了新思路。驱动新生期的再生能力机制可能涉及祖细胞、细胞外基质（ECM）、免疫调节等因素。几十年前，研究人员发现新生儿脊髓具有再生潜力，但其确切机制仍不清楚。此前，中枢神经系统（CNS）再生的一个公认障碍是髓磷脂相关蛋白和瘢痕相关分子组成的抑制性微环境。然而，减弱这些抑制性分子并没有在脊髓损伤修复中取得满意的结果。 2020年，哈佛大学何志刚团队在 Nature 期刊发表论文，揭示了新生小鼠无瘢痕脊髓修复是通过小胶质细胞分泌的细胞外基质（ECM）纤连蛋白（fibronectin，FN）实现的。这突显了新生期脊髓环境ECM对组织再生的重要性。组织脱细胞技术已成为一种有前途的细胞外基质（ECM）获取技术。通过去除细胞成分并保留组织特异性的ECM成分，脱细胞技术已被用于各种生物医学应用。然而，脊髓ECM的发育特异性功能尚未被报道。在这项研究中，研究团队探讨了早期发育阶段（新生或胚胎）和成年阶段脊髓ECM的功能。该研究发现，与成年阶段脊髓相比，早期发育阶段的脊髓具有更高的与神经发育和轴突生长相关的细胞外基质（ECM）蛋白水平，而具有较少的抑制性ECM蛋白水平。研究团队分别获取了新生兔脱细胞脊髓细胞外基质（DNSCM）和成年兔脱细胞脊髓细胞外基质（DASCM），结果显示，二者之间保留了上述差异，此外，DNSCM比DASCM更有效地促进了神经前体细胞（NPC）的增殖、迁移和神经分化，并促进了脊髓运动神经元类器官（scMN-Organs）的轴突生长和再生。通过蛋白组学分析，研究团队确定了DNSCM中的多效生长因子（Pleiotrophin，PTN）和腱糖蛋白（Tenascin，TNC）在其中发挥了关键作用。更重要的是，在脊髓损伤小鼠模型中，DNSCM促进了神经前体细胞（NPC）移植后的增殖、迁移和神经元分化，还促进了脊髓运动神经元类器官（scMN-Organs）移植后的成熟、神经突延伸和神经投射。总的来说，DNSCM与NPC/scMN-Organs协同增强了脊髓损伤后的运动功能恢复。这些结果表明了来自早期发育阶段的细胞外基质（ECM）可能对脊髓的显著再生能力有重要贡献，从而为成人脊髓损伤的治疗带来了新思路。

临床研究细胞疗法

2024-04-03

·生物探索

Cell Stem Cell | 戴建武/赵燕南阐明脊髓发育早期微环境对神经再生的作用

引言与成人脊髓组织相比，新生儿脊髓组织在损伤后表现出显著的再生能力，但细胞外基质(ECM)在这一过程中的作用仍然难以捉摸。2024年4月1日，中国科学院遗传与发育生物学研究所戴建武及赵燕南共同通讯（孙政为第一作者）在Cell Stem Cell 在线发表题为“Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids”的研究论文，该研究发现，与成年脊髓相比，早期发育的脊髓具有较高水平的与神经发育和轴突生长相关的ECM蛋白，但抑制性蛋白聚糖较少。新生儿(DNSCM)和成年(DASCM)兔的脱细胞脊髓ECM保留了这些差异。DNSCM比DASCM更能促进神经祖细胞(NPCs)的增殖、迁移和神经元分化，促进脊髓类器官轴突生长和再生。DNSCM中的多营养蛋白(PTN)和腱蛋白(TNC)被确定为这些能力的贡献者。此外，在脊髓损伤(SCI)模型中，DNSCM作为NPCs和类器官的递送载体表现出优异的性能。这表明来自早期发育阶段的ECM线索可能显著促进脊髓突出的再生能力。脊髓损伤(SCI)导致运动和感觉功能丧失，严重影响患者的生活质量。成年哺乳动物在脊髓损伤后具有有限的神经再生能力，导致永久性功能障碍。成人中枢神经系统(CNS)再生的失败是由于外部抑制分子、神经元缺乏内在再生能力和生长促进因子的缺乏。相反，某些新生哺乳动物组织在受伤后表现出强大的自我修复能力。驱动新生儿再生的可能机制涉及祖细胞、细胞外基质(ECM)、免疫调节和其他因素。研究人员在几十年前就发现了新生儿脊髓的再生潜力，尽管其确切机制尚不清楚。以前，公认的中枢神经系统再生障碍是由髓磷脂相关蛋白和瘢痕相关分子组成的抑制生态位。然而，减弱抑制分子在脊髓损伤修复中并没有产生令人满意的结果。在2022年，Li等人发现新生小鼠的无疤痕脊髓修复是由小胶质细胞分泌的ECM纤维连接蛋白(FN)实现的它强调了新生儿脊髓环境ECM对组织再生的重要性。模式图（Credit: Cell Stem Cell）ECM对细胞活力至关重要，提供结构支持和调节信号转导。ECM的组成在不同的发育阶段和病理条件下是不同的。这可能是新生儿和成人在再生能力上存在差异的原因早期发育阶段的ECM可以有效地指导成人组织再生。例如，新生儿心脏ECM诱导心肌细胞增殖，减少瘢痕形成，并增强成人心肌梗死后的功能恢复。组织脱细胞已成为获得ECM的一种很有前途的技术。通过去除细胞成分并保留组织特异性ECM成分，脱细胞已用于各种生物医学应用。然而，脊髓ECM的发育特异性功能尚未被报道。该研究进行了一项研究，探讨脊髓ECM在早期发育阶段(新生儿或胚胎)和成人阶段的功能。研究结果表明，早期发育的脊髓ECM可能为重建再生生态位提供了一种策略，以应对成人脊髓损伤的挑战。研究发现DNSCM向内源性轴突传递生化信号，促进轴突再生，促进移植物与宿主神经之间的整合，从而增强运动功能的恢复，即使在完全性脊髓损伤的挑战性微环境中也是如此。原文链接https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00089-4责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

细胞疗法

2024-02-05

·Science Daily

The influence of the cellular environment on vision

The processing of visual information begins with a targeted and balanced communication between nerve cells in the retina via synapses. Proteins in the vicinity of nerve cells play an important role in the development, maturation, and function of these synapses. A research team was able to show that the combined loss of four proteins leads to a severe impairment of the function of the retina, reduced visual movement processing and significant synaptic changes. The research team investigated the four extracellular matrix proteins Brevican, Neurocan, Tenascin-C and Tenascin-R, which occur in the cell environment of nerve cells of the retina. "Their precise role in the retina has not yet been sufficiently investigated," explains Jacqueline Reinhard-Recht. The researchers therefore studied the visual function of so-called knockout mice, which were genetically modified in such a way that their bodies could not produce the four mentioned proteins. Through electroretinogram analyses, the research team was able to show that rod photoreceptors and bipolar cells in the knockout mice exhibit functional deficits in visual processing. "Interestingly, we were also able to find significant limitations in visual movement processing in the knockout mice compared to control animals," says Jacqueline Reinhard-Recht. Mice lacking only the proteins tenascin-C or tenascin-R also display losses in visual motion processing, but much weaker. "This shows that the cumulative loss of four matrix proteins reinforces optomotor limitations," says the researcher. Matrix remodeling and imbalance in synaptic signaling Studies on the retina of knockout mice also revealed changes in various matrix molecules and synapses. "In particular, there was an imbalance of inhibitory and excitatory synapses," says Jacqueline Reinhard-Recht. "Overall, the research data indicate that the four matrix proteins Brevican, Neurocan, Tenascin-C and Tenascin-R are important modulators of synaptic signaling in the retina." "The research data contribute to a much better understanding of the complex molecular mechanisms of visual processing. In the future, these findings could offer new approaches for the development of therapeutic interventions for visual function disorders."

临床结果