预约演示

更新于：2025-05-07

ITGA9

更新于：2025-05-07

基本信息

别名

ALPHA-RLC、Integrin alpha-9、Integrin alpha-RLC

+ [6]

简介

Integrin alpha-9/beta-1 (ITGA9:ITGB1) is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion (By similarity). Integrin ITGA9:ITGB1 represses PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via its interaction with SVEP1, thereby inhibiting vasocontraction (PubMed:35802072).

关联

项与 ITGA9 相关的药物

GND-001

靶点

ITGA9

作用机制

ITGA9拮抗剂

在研机构

Kaken Pharmaceutical Co., Ltd. [+1]

原研机构

Kidswell Bio Corp.

在研适应症

免疫系统疾病 [+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

ASP-5094

靶点

ITGA9

作用机制

ITGA9拮抗剂

在研机构-

原研机构

Astellas Pharma, Inc.

在研适应症-

非在研适应症

类风湿关节炎

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 ITGA9 相关的临床试验

NCT03257852

/ Completed临床2期

A Phase 2a, Randomized, Placebo-Controlled, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate

The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of ASP5094 in patients with rheumatoid arthritis (RA) treated with background methotrexate (MTX).

开始日期2017-09-29

申办/合作机构

Astellas Pharma, Inc.

NCT02698657

/ Completed临床1期

A Phase 1, Randomized, Placebo-controlled, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP5094 Following Multiple Intravenous Doses in Subjects With Rheumatoid Arthritis on Methotrexate

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of multiple ascending intravenous doses of ASP5094 in male and female subjects with rheumatoid arthritis (RA) on methotrexate (MTX).

开始日期2016-02-23

申办/合作机构

Astellas Pharma Global Development, Inc.

100 项与 ITGA9 相关的临床结果

登录后查看更多信息

100 项与 ITGA9 相关的转化医学

登录后查看更多信息

0 项与 ITGA9 相关的专利（医药）

登录后查看更多信息

165

项与 ITGA9 相关的文献（医药）

2025-04-09·The Journal of Neuroscience

The Medial Olivocochlear Efferent Pathway Potentiates Cochlear Amplification in Response to Hearing Loss

Article

作者: Wang, Juemei ; Quiñones, Patricia M ; Srivastava, Hemant ; Dewey, James B ; Serafino, Michael J ; Macias-Escriva, Frank ; Applegate, Brian E ; Oghalai, John S ; McGinley, Matthew J ; Kim, Bong Jik ; Cobo-Cuan, Ariadna ; Morán, Marcela A ; Walker, Clayton B ; Pei, Michelle

The mammalian cochlea receives efferent feedback from the brain. Many functions for this feedback have been hypothesized, including on short timescales, such as mediating attentional states, and long timescales, such as buffering acoustic trauma. Testing these hypotheses has been impeded by an inability to make direct measurements of efferent effects in awake animals. Here, we assessed the role of the medial olivocochlear (MOC) efferent nerve fibers on cochlear amplification by measuring organ of Corti vibratory responses to sound in both sexes of awake and anesthetized mice. We studied long-term effects by genetically ablating the efferents and/or afferents. Cochlear amplification increased with deafferentation using VGLUT3 −/− mice, but only when the efferents were intact, associated with increased activity within OHCs and supporting cells. Removing both the afferents and the efferents using VGLUT3 −/− Alpha9 −/− mice did not cause this effect. To test for short-term effects, we recorded sound-evoked vibrations while using pupillometry to measure neuromodulatory brain state. We found no state dependence of cochlear amplification or of the auditory brainstem response. However, state dependence was apparent in the downstream inferior colliculus. Thus, MOC efferents upregulate cochlear amplification chronically with hearing loss, but not acutely with brain state fluctuations. This pathway may partially compensate for hearing loss while mediating associated symptoms, such as tinnitus and hyperacusis.

2024-11-01·Gene

Integrin-α9 overexpression underlies the niche-independent maintenance of leukemia stem cells in acute myeloid leukemia

Article

作者: Niibori-Nambu, Akiko ; Tergaonkar, Vinay ; Chooi, Jing Yuan ; Wang, Chelsia Qiuxia ; Goh, Yufen ; Yang, Henry ; Osato, Motomi ; Taniuchi, Ichiro ; Tham, Cheng-Yong ; Fam, Wee Nih ; Sonoki, Takashi ; Fullwood, Melissa Jane ; Suda, Toshio ; Hosoi, Hiroki ; Tan, Darren Qiancheng ; Tng, Jiaqi ; Chng, Wee Joo ; Chin, Desmond Wai Loon ; Nah, Giselle Sek Suan ; Li, Shang ; Takizawa, Hitoshi ; Cirovic, Branko ; Sashida, Goro

Leukemia stem cells (LSCs) are widely believed to reside in well-characterized bone marrow (BM) niches; however, the capacity of the BM niches to accommodate LSCs is insufficient, and a significant proportion of LSCs are instead maintained in regions outside the BM. The molecular basis for this niche-independent behavior of LSCs remains elusive. Here, we show that integrin-α9 overexpression (ITGA9 OE) plays a pivotal role in the extramedullary maintenance of LSCs by molecularly mimicking the niche-interacting status, through the binding with its soluble ligand, osteopontin (OPN). Retroviral insertional mutagenesis conducted on leukemia-prone Runx-deficient mice identified Itga9 OE as a novel leukemogenic event. Itga9 OE activates Akt and p38MAPK signaling pathways. The elevated Myc expression subsequently enhances ribosomal biogenesis to overcome the cell integrity defect caused by the preexisting Runx alteration. The Itga9-Myc axis, originally discovered in mice, was further confirmed in multiple human acute myeloid leukemia (AML) subtypes, other than RUNX leukemias. In addition, ITGA9 was shown to be a functional LSC marker of the best prognostic value among 14 known LSC markers tested. Notably, the binding of ITGA9 with soluble OPN, a known negative regulator against HSC activation, induced LSC dormancy, while the disruption of ITGA9-soluble OPN interaction caused rapid cell propagation. These findings suggest that the ITGA9 OE increases both actively proliferating leukemia cells and dormant LSCs in a well-balanced manner, thereby maintaining LSCs. The ITGA9 OE would serve as a novel therapeutic target in AML.

2024-06-01·Regenerative Therapy

METTL3 promotes the osteogenic differentiation of periosteum-derived MSCs via regulation of the HOXD8/ITGA5 axis in congenital pseudarthrosis

Article

作者: Yan, An ; Liu, Yaoxi ; Tan, Qian ; Xiao, Han ; Ye, Weihua ; Zhu, Guanghui ; Liu, Zheng

BackgroundCongenital pseudarthrosis of the tibia (CPT) is a dominant health challenge in pediatric orthopedics. The essential process in the development of CPT is the limited capacity of mesenchymal stem cells (MSCs) derived from CPT to undergo osteogenic differentiation. Our research aimed to elucidate the role and mechanism of methyltransferase-like 3 (METTL3) in the osteogenic differentiation process of CPT MSCs.MethodsThe osteogenic differentiation medium was used to culture MSCs, and the detection of osteogenic differentiation was performed using Alizarin Red S and alkaline phosphatase (ALP) assays. Gene or protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, or immunofluorescence (IF) staining. The m⁶A modification of Homeobox D8 (HOXD8) was verified by methylated RNA immunoprecipitation (MeRIP) assay. Interactions between METTL3 and HOXD8 or HOXD8 and integrin alpha 5 (ITGA5) promoter were validated by the luciferase reporter gene, RIP, and chromatin immunoprecipitation (ChIP) assays.ResultsMETTL3 overexpression enhanced CPT MSCs' osteogenic differentiation. METTL3 stabilized the HOXD8 in an m⁶A-dependent manner. Moreover, the overexpressed ITGA5 up-regulated the CPT MSCs' osteogenic differentiation. Further, HOXD8 could transcriptionally activate ITGA5. METTL3 increased the transcription of ITGA5 via HOXD8 to enhance the osteogenic differentiation of CPT MSCs.ConclusionMETTL3 promoted osteogenic differentiation via modulating the HOXD8/ITGA5 axis in CPT MSCs.

项与 ITGA9 相关的新闻（医药）

2025-04-01

·生物谷

Nature Communications | 四川大学李中瀚教授课题组建立基于人多能干细胞的SOX9+生骨节前体细胞分化体系

骨骼系统由骨和软骨组织构成，为人体提供支撑、保护及肌肉附着点，支持运动。骨发育相关疾病，如成骨不全症、先天性脊椎骨骺发育不良等，严重影响生活质量，甚至导致胎儿死亡，是重要的基础医学问题。然而，由于人类骨组织获取困难，且缺乏具有自发育能力的器官模型，显著制约了我们对于人源骨组织发育原理和骨发育相关疾病分子机制的解析。因此，建立高效、均一的分化体系以获取种子细胞，并构建精准的骨骼发育模型，对揭示骨发育调控机制及挖掘治疗靶点具有重要基础科学意义。人类骨发育主要通过膜内成骨和软骨内成骨两种方式。大部分骨骼，如胸骨、四肢骨等，通过软骨内成骨发育。该过程始于间质细胞凝集形成软骨原基，随后经历软骨细胞肥大、血管入侵等阶段，最终形成具有骨髓腔的骨组织。生长板结构是骨骼干细胞的主要驻留区域，肥大软骨则调控基质矿化、分泌血管内皮生长因子，并分化为成骨细胞等，构建支持造血的微环境。尽管利用间充质干细胞、人多能干细胞等在骨组织构建中取得了一定进展，但成体干细胞存在发育谱系不明确、异质性高等问题，限制了其应用。现有基于人多能干细胞的模型耗时较长，且无法模拟早期发育过程及生长板形成。因此，构建更接近体内发育进程的全功能人类软骨内成骨模型仍是研究热点和难点。2025年3月21日，四川大学李中瀚教授课题组在Nature Communications上发表题为“Recapitulation of endochondral ossification by hPSC-derived SOX9+ sclerotomal progenitors”的研究论文。该研究开发了一种高效分化体系，成功从人多能干细胞（hPSCs）中以>99%的分化效率获得了SOX9+生骨节间质前体细胞（SOX9+ scl-progenitors），解决了传统分化过程中的细胞异质性问题。这些前体细胞具有优异的成软骨和成骨分化潜能。通过无血清谱系定向诱导方法，可分别发育为软骨前体细胞和（软骨内成骨定向的）早期软骨细胞。其中经成球培养形成的软骨前体细胞移植后发育为透明软骨组织，可介导免疫缺陷小鼠关节缺损修复；而在高密度贴壁培养条件下，SOX9+ scl-progenitors经间质凝集发育为（软骨内成骨定向的）早期软骨细胞，移植后通过软骨原基形成、肥大软骨分化、血管侵入等过程发育为含髓腔的骨组织，高度模拟软骨内成骨过程。更重要的是，两种前体细胞有序融合后，能够自发形成具备极性伸长能力的生长板样结构，其分子和细胞组成与胚胎长骨组织高度相似，且形成的骨组织具有人类原代组织的力学性能。此外，该研究鉴定了ITGA9作为SOX9+ scl-progenitors的表面标志物，为骨骼发育研究和生物工程提供了重要的种子细胞来源。同时，建立了SOX9+ scl-progenitors的无血清扩增体系，可在2个月内实现约15,000倍的扩增，为骨发育研究提供了规模化的细胞来源。综上，本研究提供了一套基于hPSCs的软骨内骨化及生长板形成的模拟体系，为研究骨-造血系统微环境及骨发育缺陷疾病机制提供了新范式。在本研究中，四川大学博士生熊靖飞为论文第一作者，四川大学李中瀚教授、殷旖珂副教授作为该论文的共同通讯作者。该研究获得了科技部重点研发计划“干细胞研究与器官修复”和“干细胞及转化研究”项目、国家自然科学基金、国家特聘计划青年项目、四川省重大科技专项等的资助。论文链接：https://doi.org/10.1038/s41467-025-58122-9本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

2022-07-25

·生物谷

Br J Pharmacol: SVEP1和整合素α4β1和α9β1在降低血管平滑肌细胞收缩中的新作用

血管张力由血管平滑肌细胞(VSMCs)的相对收缩状态调节。一些整合素通过L型电压门控钙通道(VGCC)调节钙内流，直接调节VSMC收缩。血管张力由血管平滑肌细胞(VSMCs)的相对收缩状态调节。一些整合素通过L型电压门控钙通道(VGCC)调节钙内流，直接调节VSMC收缩。编码整合素α9亚基α9β1的ITGA9和整合素α9β1的配体SVEP1的遗传变异与血压升高有关，然而，SVEP1和整合素α9β1都没有报道在血管调节中的作用。研究者确定了sVEP1和整合素α-9-β-1是否具有调节血管平滑肌细胞收缩的作用。图片来源: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15921 近日，来联合王国自莱斯特大学和国家健康研究所莱斯特生物医学研究中心的研究者们在Br J Pharmacol杂志上发表了题为“SVEP1 regulates GPCR-mediated vasoconstriction via integrin α9β1 and α4β1”的文章，该研究揭示了SVEP1和整合素α4β-1和α9β-1在降低血管平滑肌细胞收缩中的新作用。这可能为SVEP1和ITGA9基因座与血压风险的遗传关联提供解释。研究者使用免疫沉淀法和细胞结合实验证实SVEP1和整合素结合。人诱导多能干细胞来源的VSMCs用于体外[Ca~(2+)]i研究，Svep1+/-基因敲除小鼠模型的主动脉用于线状肌图术以测量血管收缩。研究者证实了SVEP1与整合素α9β1的连接，并发现SVEP1与整合素α4β1直接结合。研究者证实抑制SVEP1、整合素α4β1或α9β1可显著增加VSMC对GαQ/11-血管收缩药的[Ca~(2+)]i释放。与同窝小鼠相比，Svep1+/-小鼠的血管对U46619的收缩更大，或者当整合素α4β1或α9β1被抑制时，这种反应在整个血管中得到了证实。抑制研究表明，这种作用是通过VGCCs、PKC和Rho A/Rho激酶依赖的机制来实现的。 SVEP1调节GPCR介导的血管收缩U46619与Tax2R结合以激活GαQ和G12/13信号的拟议模型示意图图片来源: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15921 总之，本研究首次描述了细胞外基质蛋白SVEP1如何通过整合素α4β1和/或α9β1影响通过VGCC减少钙内流和降低钙敏感性的途径来降低血管平滑肌细胞的收缩能力，从而在细胞外环境和血管平滑肌细胞收缩之间提供了新的联系。（生物谷 Bioon.com）参考文献 Morris GE et al. SVEP1 regulates GPCR-mediated vasoconstriction via integrin α9β1 and α4β1. Br J Pharmacol. 2022 Jul 8. doi: 10.1111/bph.15921.