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更新于：2025-05-07

α10β1

更新于：2025-05-07

基本信息

别名-

简介-

关联

项与 α10β1 相关的药物

Anti-α-10(Cartela)

靶点

α10β1

作用机制

α10β1拮抗剂

在研机构

Cartela AB

原研机构

Cartela AB

在研适应症

类风湿关节炎

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

TARG-10

靶点

α10β1

作用机制

α10β1拮抗剂

在研机构

Targinta AB

原研机构

Cartela AB

在研适应症

胶质母细胞瘤 [+1]

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

TARG-9

靶点

α10β1

作用机制

α10β1拮抗剂

在研机构

Targinta AB

原研机构

Targinta AB

在研适应症

胶质母细胞瘤 [+1]

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 α10β1 相关的临床结果

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100 项与 α10β1 相关的转化医学

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0 项与 α10β1 相关的专利（医药）

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138

项与 α10β1 相关的文献（医药）

2025-03-01·Journal of Investigative Dermatology

Integrin α11β1 as a Key Collagen Receptor in Human Skin Dermis: Insight into Fibroblast Function and Skin Dermal Aging

Article

作者: Fisher, Gary J ; Quan, Taihao ; Qin, Zhaoping ; He, Tianyuan

Collagen-binding integrins play a crucial role in facilitating fibroblast-collagen interactions and regulating cellular functions. In this study, we identified that among 4 collagen-binding integrins, integrin α11 was the predominant type in human skin dermal fibroblasts and that loss of integrin α11 expression contributed to skin dermal aging. Integrin α11β1 was critical for regulating fibroblast-collagen interactions, including cell adhesion, spreading, morphology, mechanical tension, and the production of collagenous extracellular matrix. TGF-β was recognized as the primary regulator of integrin α11 expression. Notably, dermal fibroblasts in aged human skin demonstrated impaired TGF-β signaling, which coincided with a loss of integrin α11 expression, whereas the expression of other collagen-binding integrins remained unchanged. Similarly, in senescent dermal fibroblasts in vitro, impaired TGF-β signaling was associated with a significant reduction in integrin α11 expression, whereas other collagen-binding integrins were upregulated or unaffected. Furthermore, collapsed dermal fibroblasts, a key characteristic of dermal fibroblasts in aged human skin, specifically downregulated integrin α11, whereas other collagen-binding integrins were upregulated or remained unchanged. These findings suggest a negative feedback loop in which an impaired TGF-β-integrin α11β1 axis and fibroblast collapse promote dermal aging in human skin. This self-reinforcing cycle reflects the progressive and unidirectional nature of biological aging.

2025-02-07·Investigative Ophthalmology & Visual Science

Extracellular Matrix Stiffness Modulates Myopia Scleral Remodeling Through Integrin/F-Actin/YAP Axis

Article

作者: Liu, Xin ; Liu, Yuying ; Zhu, Chengcheng ; Ke, Bilian ; Yuan, Ying ; Wu, Yue

PurposeScleral extracellular matrix (ECM) remodeling and weakened scleral stiffness are characteristic of myopia. The purpose of this study was to investigate the precise underlying mechanisms of scleral remodeling regulated by mechanical signals emanating from the ECM.MethodsThe expression and regulation of YES-associated protein (YAP) were confirmed in human samples or guinea pig myopia models by Western blot (WB) or ELISA. To mimic the biomechanical microenvironment associated with myopia, stiff (50 kPa) and soft (8 kPa) substrates were established. The underlying mechanisms were further investigated by quantitative real-time RT-PCR, WB, and fluorescence staining in cells treated with siRNAs, plasmids or inhibitors. In vivo, a YAP activator, inhibitor and F-actin polymerization facilitator were applied to evaluate their therapeutic significance for myopia.ResultsOur findings revealed that YAP expression is decreased in the sclera of guinea pigs and humans with myopia. Under mechanical stimuli, YAP functions as a mediator, transducing mechanical signals and modulating collagen expression. Furthermore, integrin α1β1 acts as a regulator of YAP and operates through modification of the F-actin cytoskeleton. Specifically, in response to mechanical forces, integrin α1β1 modulates F-actin restructuring. This modified actin cytoskeletal architecture subsequently facilitates the nuclear translocation of YAP, ultimately leading to the suppression of COL1A1 expression.ConclusionsOur results suggest that the integrin α1β1-F-actin-YAP-COL1A1 axis constitutes a vital regulatory mechanism intrinsically associated with the pathogenesis of myopia.

2025-02-01·Experimental Cell Research

Matrix-mediated activation of murine fibroblast-like synoviocytes

Article

作者: Zeinert, Isabel ; Brachvogel, Bent ; Zaucke, Frank ; Baar, Till ; Pap, Thomas ; Mahabir, Esther ; Schmidt, Luisa ; Krieg, Thomas ; De Giuseppe, Anna ; Eckes, Beate ; Gatto, Giulio ; Krüger, Marcus ; Korb-Pap, Adelheid

Fibroblast-like synoviocytes (FLS) are key cells promoting cartilage damage and bone loss in rheumatoid arthritis (RA). They are activated to assume an invasive and migratory phenotype. While mechanisms of FLS activation are unknown, evidence suggests that pre-damaged extracellular matrix (ECM) of the cartilage can trigger FLS activation. Integrin α11β1 might be involved in the activation, as it is increased in RA patients and hTNFtg mice, an RA mouse model. We treated murine chondrocytes with TNFα to produce a damaged, RA-like matrix. Comparison to healthy chondrocyte matrix revealed decreased ECM proteins, e.g. collagens and proteoglycans, increased matrix-degrading proteins and elevated levels of inflammatory cytokines. FLS responded to the damaged chondrocyte matrix with a matrix-remodeling and pro-inflammatory phenotype characterized by a gene signature involved in matrix degradation and increased production of CLL11 and CCL19. Damaged chondrocyte matrix stimulated increased Itga11 expression in FLS, correlating with the increased α11β1 amounts in RA patients. FLS deficient in integrin α11β1 released lower amounts of inflammation-associated cytokines. Our results demonstrate differences in healthy and RA-like chondrocyte ECM and distinctly different responses of wt FLS to damaged versus healthy ECM.

项与 α10β1 相关的新闻（医药）

2024-02-26

·生物探索

Sci Transl Med | 余家阔/聂广军团队合作开发仿生纳米药物，用于骨关节炎治疗

引言骨关节炎（OA）是一种以关节软骨渐进性退化为特征的慢性关节疾病。在疾病修复药物的开发中，有效传递给软骨细胞是一个挑战。关节的独特结构促进了药物通过滑膜液的快速清除，而密集且无血管的软骨细胞外基质（ECM）限制了药物的渗透。2024年2月21日，国家纳米科学中心聂广军团队与北京大学第三医院余家阔团队合作在Science Translational Medicine在线发表题为“Chondrocyte membrane–coated nanoparticles promote drug retention and halt cartilage damage in rat and canine osteoarthritis”的研究论文，该研究展示了以软骨细胞膜（CM）包被的聚乳酸-聚乙二醇酸（PLGA）纳米颗粒与未包被的纳米颗粒相比，在体外更易被大鼠软骨细胞优先摄取。CM-NPs的内部化主要通过E-钙粘蛋白介导、网格蛋白覆盖的细胞吞噬作用和微囊泡内吞作用来介导。这些CM-NPs在大鼠膝关节的软骨ECM上粘附，在体内深入渗透软骨基质，并具有超过34天的驻留时间。模拟滑膜液清除研究表明，载有Wnt通路抑制剂adavivint（CM-NPs-Ada）的CM-NPs延迟了大鼠和人类软骨细胞及软骨外植体在炎症条件下的分解代谢。在大鼠OA的手术模型中，载药的CM-NPs有效恢复了步态，减轻了关节周围骨重塑，并提供了对软骨退变的保护作用。在前交叉韧带切断的犬模型中，CM-NPs-Ada也减轻了OA的进展。这些结果证明了使用软骨细胞膜包被的纳米颗粒来改善抗OA药物的药代动力学和疗效的可行性。骨关节炎（OA）是一种高度普遍的退行性关节疾病，全球有超过5亿人受其影响，造成了巨大的社会和经济负担。OA的特征是局部进行性关节软骨退化、关节炎症和病理性骨下重建，导致慢性疼痛和最终关节功能失败。对于OA患者的症状，有各种干预方法可供选择；然而，目前尚无可用的改变疾病进程的治疗方法。一些生物制剂和小分子药物，如促进生长因子、基质降解酶抑制剂和抗炎分子，在临床前研究中显示出抑制软骨退化的潜力。然而，不幸的是，这些药物候选物未能从临床试验进展到临床实践，因为它们对患者的益处有限。在OA治疗的药物治疗中，一个主要挑战是维持足够的有效药物浓度，以诱导所需的生物学反应。由于关节软骨缺乏血管，全身药物给药导致软骨的分布不足。直接关节内注射是增加关节生物利用度、减少全身不良反应的合理方法；然而，即使是局部给药仍然不足够。药物通过滑膜毛细血管和淋巴引流迅速从关节腔中清除，关节中的停留时间短至1到4小时。残留在关节内的极少量药物被关节软骨外基质所排除。关节软骨外基质由软骨细胞合成，由胶原纤维、聚糖蛋白和其他几十种细胞外大分子组成。因此，ECM不仅保护着软骨细胞，而且对于治疗分子从滑膜液渗透并进一步被软骨细胞内化构成了重要的空间障碍。结合临床医生需要最大程度地减少由于反复关节内注射而导致的感染风险，滑膜液中药物半衰期短和不足够扩散到软骨的两个重要生物学屏障，限制了连续治疗，从而影响了长期效果。因此，治疗OA的理想药物输送平台能够在被清除之前足够渗透软骨并结合软骨内的部位，将屏障转化为持续的组织内递送药物的药库。软骨细胞合成并维持ECM以抵抗物理变形，并表达许多细胞表面标志物与周围ECM相互作用。在软骨细胞和基质之间的相互作用中，膜表面的粘附受体在介导细胞与ECM之间的相互作用中起着重要作用。例如，II型胶原（COLII）具有α1β1、α2β1和α10β1整合素的结合位点，而纤维连接蛋白结合整合素包括α3β1和αVβ1。软骨细胞膜（CM）CD44负责在ECM中特异性结合透明质酸。CM-NPs保留了大鼠原代软骨细胞膜的蛋白谱（Credit: Science Translational Medicine ）通过将亲和配体连接到药物载体的表面，可以实现活性纳米颗粒靶向，从而通过配体-受体相互作用靶向软骨细胞或ECM。功能化的聚合物纳米颗粒与II型胶原抗体和胶原结合肽结合后，可以特异性地结合到软骨并将治疗药物传递到软骨细胞中。随着OA中软骨损伤的增加，软骨成分（如蛋白多糖和胶原）逐渐丧失，使得 passi目标的结合能力和单一配体修饰的活性靶向策略受到限制。为了克服现有策略在靶向软骨内个别组分方面的局限性，混合纳米颗粒融合多种亲和配体可能提供了比单一配体修饰的靶向策略更优越的结合能力。软骨细胞-基质相互作用的独特性质启发作者直接利用天然衍生的CM涂层作为赋予软骨药物输送系统增强特异性和结合能力的手段。在此，作者设计了工程化的CM修饰的聚乳酸-聚乙二醇酸（PLGA）纳米颗粒（CM-NPs），并研究了它们作为OA管理的药物储库的用途。通过在PLGA核心表面显示软骨细胞质膜，CM-NPs模拟了软骨细胞，并结合到软骨ECM上，以实现药物的有效保留和渗透，以达到同种型软骨细胞并最终引发持续的软骨保护。原文链接https://www.science.org/doi/10.1126/scitranslmed.adh9751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Nature | 癌症与神经系统的致命舞蹈

临床研究