更新于：2024-11-01

IGFBP5

更新于：2024-11-01

基本信息

别名

IBP-5、IBP5、IGF-binding protein 5

+ [5]

简介

IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.

关联

项与 IGFBP5 相关的药物

US20230192827

专利挖掘

靶点

IGFBP5

作用机制-

在研机构

Enthera Srl初创企业

原研机构

Enthera Srl初创企业

在研适应症

免疫系统疾病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

OGX-225

靶点

IGFBP2 x IGFBP5

作用机制

IGFBP2抑制剂 [+1]

在研机构-

原研机构

Ionis Pharmaceuticals, Inc.

在研适应症-

非在研适应症

乳腺癌

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

OGX-133

靶点

IGFBP5

作用机制

IGFBP5抑制剂

在研机构-

原研机构

OncoGenex Technologies, Inc.

在研适应症-

非在研适应症

前列腺癌

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

100 项与 IGFBP5 相关的临床结果

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100 项与 IGFBP5 相关的转化医学

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0 项与 IGFBP5 相关的专利（医药）

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1,536

项与 IGFBP5 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Mir-204-5p alleviates mitochondrial dysfunction by targeting IGFBP5 in diabetic cataract

Article

作者: Wang, Xiaolei ; Zang, Xinyi ; Xie, Jin ; Chen, Peng ; Mao, Shilan ; Dai, Yunhai ; Liu, Wenhui ; Cao, Rui

BACKGROUNDCataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive.METHODS AND RESULTThe mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model.CONCLUSIONSOur results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.

2024-12-01·Molecular Biology Reports

High-intensity interval training enhances mRNA expression of IGF1Ea in rat Achilles tendon

Article

作者: Tsuchiya, Yoshifumi ; Takakura, Hisashi ; Osawa, Seita ; Izawa, Tetsuya

High-intensity interval training (HIIT) reportedly enhances the functional properties of the musculoskeletal system. However, the effects of HIIT on tendons remain unclear. Sixteen male rats were randomly assigned to the control (Con) or HIIT group (n = 8 in each group). Rats in the HIIT group executed the HIIT program consisting of 2.5 min treadmill running and 4.5 min rests between the bouts, 5 days per week for 9 weeks. Running speed, number of sets, and inclination were incrementally increased during the training period. Histological analysis revealed no apparent morphological changes in the extracellular matrix structure or nuclei of tenocytes between the groups. Real-time reverse transcription polymerase chain reaction analysis revealed that Igf1Ea mRNA expression was enhanced in the HIIT group. Furthermore, Igfbp5 mRNA expression tended to be higher in the HIIT group. The 9-week HIIT program enhanced tenogenic Igf1Ea mRNA expression.

2024-11-01·Breast Cancer Research and Treatment

A novel role of IGFBP5 in the migration, invasion and spheroids formation induced by IGF-I and insulin in MCF-7 breast cancer cells

Article

作者: Torres-Alamilla, Pablo ; Cortes-Reynosa, Pedro ; Rodríguez-Rojas, Karem ; Salazar, Eduardo Perez ; Rodríguez-Ochoa, Nínive

AbstractPurposeThe insulin-like growth factor (IGF) system includes IGF-I, IGF-II insulin and their membrane receptors. IGF system also includes a family of proteins namely insulin-like growth factor-binding proteins (IGFBPs) composed for six major members (IGFBP-1 to IGFBP6), which capture, transport and prolonging half-life of IGFs. However, it has been described that IGFBPs can also have other functions.MethodsIGFBP5 expression was inhibited by shRNAs, migration was analyzed by scratch-wound assays, invasion assays were performed by the Boyden chamber method, spheroids formation assays were performed on ultra-low attachment surfaces, expression and phosphorylation of proteins were analyzed by Western blot.ResultsIGFBP5 is a repressor of IGF-IR expression, but it is not a repressor of IR in MCF-7 breast cancer cells. In addition, IGFBP5 is a suppressor of migration and MMP-9 secretion induced by IGF-I and insulin, but it does not regulate invasion in MCF-7 cells. IGFBP5 also is a repressor of MCF-7 spheroids formation. However treatment with 340 nM rescues the inhibitory effect of IGFBP in the MCF-7 spheroids formation.ConclusionIGFBP5 regulates IGF-IR expression, migration and MMP-9 secretion induced by IGF-I and/or insulin, and the spheroids formation in MCF-7 breast cancer cells.

项与 IGFBP5 相关的新闻（医药）

2023-06-08

·生物谷

EVTOP技术研究微升生物体液循环EV中的磷酸化蛋白质组特征

一、摘要|导读：许多生物过程离不开动态的蛋白质磷酸化调节，因此监测循环生物体液中与疾病相关的磷酸化事件意义非凡，然而，由于磷酸酶的存在使得监测生物体液中磷酸化蛋白的变化极具挑战性。近期，东南大学W. Andy Tao教授团队在Angewandte Chemie在线发表了题为Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids through Functionally Tunable Paramagnetic Separation的研究文章。该研究介绍了一种功能可调的材料和方法：从细胞外囊泡到磷酸化蛋白-------EVTOP(Extracellular Vesicles To Phosphoproteins)，它实现了一步法分离、提取和消化EV蛋白，并富集了磷酸化肽段，而且只需微量的起始生物液。用钛(IV)离子功能化的磁珠和穿膜肽八精氨酸（ R8+）有效地分离EV，同时R8+提供了亲水表面以在裂解过程中保留EV蛋白。随后磁珠上消化的同时将EVTOP转化为纯Ti(IV)离子表面，有效地富集了磷酸化肽。这个简化的超灵敏平台能够仅用几个μL血浆就能定量500个独特的EV磷酸化肽，用100μL脑脊液（CSF）就能定量1,200多个磷酸化肽。该团队还探讨了小容量CSF监测原发性中枢神经系统淋巴瘤(PCNSL，Primary Central Nervous System Lymphoma)化疗效果的临床应用，为临床的广泛应用提供了有力工具。二、实验|设计和方法图1. 实验流程示意图上图简要展示了该团队从微量体液中分离肠道病毒并原位富集磷酸化肽用于深度磷酸化蛋白质组图谱的研究方法。三、结果|创新点图2. 关于EVTOP磁珠制备及EV分离的表征EVTOP设计充分利用了EV的双层磷脂层结构，包括自组装的疏水尾部和亲水性磷酸盐头部，并考虑了直接在珠上的样品的下游工艺。该方法特殊在：(I)磁珠被Ti(IV)离子和 R8+功能化，为有效分离EV提供协同亲和力；(Ⅱ)带正电的Ti(IV)离子和 R8+通过疏水-亲水(HILIC)相互作用提供亲水表面，在EV裂解过程中保留EV蛋白；(Ⅲ)珠上消化产生多肽并同时将 R8+从珠子上切割下来；(Ⅳ)EVTOP只在表面吸附了Ti(IV)离子，实现了磷酸化肽在LC-MS分析中的特异性富集化。EVTOP的主要特点是能够通过同一磁珠上官能团的相互作用和转化，实现从生物液体到浓缩EV磷酸化肽的所有样品制备步骤。一步法在MS分析前不需要任何清理或除盐步骤，最大限度地减少了样品损失，从而能够利用微升临床样品实现极其灵敏和定量的磷酸化蛋白质组学。该团队考察了三种功能化磁珠以及超速离心法对EV的捕获。根据三种EV标志物(CD9、Flotillin 1和β-Actin)的WB结果，EV分离效率的顺序是EVTOP>仅R8+>仅Ti(IV)>超速离心法，其中EVTOP最有效。图3. 胰酶处理EVTOP磁珠对EV捕获率的影响经胰酶消化后的EVTOP磁珠的捕获EV效率明显下降，同时Zeta电位发生变化。WB结果和质谱学鉴定进一步证实了R8+和Ti(IV)离子的重要作用。通过在胰酶消化过程中同时切割R8+，EVTOP被转化为纯Ti(IV)离子磁珠。PCNSL是一种罕见的仅限于中枢神经系统的非霍奇金淋巴瘤亚型，作为一种具有复杂发病机制的高度异质性疾病，PCNSL的分子特征至关重要，CSF是准确评估疾病的理想微创生物液体。以前使用大量CSF样本的尝试只发现了少量的磷酸化蛋白。为了展示EVTOP的临床应用，该团队首先使用EVTOP方法分析了21例PCNSL患者和21例匹配的非PCNSL对照CSF样本的EV磷酸化蛋白质组学定量。图4.临床CSF样本本分析过程及结果。该团队总共从CSF样本 EVs中鉴定出3,344个磷酸化肽，代表689个磷酸化蛋白，其中160个磷酸化蛋白在PCNSL患者中上调。GO、KEGG途径和PPI分析表明，上调的磷酸化蛋白参与神经肽激素活性、透明质酸结合和多种信号途径，如Wnt信号和PI3K-Akt途径。其中一些上调的磷酸化蛋白被报道为PCNSL和其他癌症的潜在生物标记物，如骨桥蛋白(SPP1)，组织蛋白B(CTSB)，纤维连接蛋白(FN1)，CD44，Tenascin-X(TNX)，肉豆蔻酰化丙氨酸C-激酶底物(Marcks)和Testican-3(SPOCK3)。图5.已识别的EV磷酸化蛋白作为潜在的生物标志物评估PCNSL化疗结果的可行性。该团队选择了11名PCNSL患者的独立队列，这些患者最初接受大剂量甲氨蝶呤治疗，总体临床反应良好。分别于化疗前和化疗后采集CSF标本100ug。然后对CSF样本进行EVTOP程序以获得EV磷酸化肽。使用TimeTOF Pro仪上的平行反应监测和平行累积-连续碎裂(PRM-FASEF)相结合的方法来监测化疗前后这些上调的磷酸化蛋白的强度变化。排除了重复性相对较差、产物离子覆盖率较低、缺乏生物学意义(无疾病或相关生物途径关联)的磷酸化肽。发现10个磷酸化蛋白【SPP1、促甲状腺激素释放激素原(TRH)、Tenascin-C(TNC)、硒蛋白P(SEPP1)、纤维蛋白原β链(FGB/FIBB)、层粘连蛋白β1(Lamb1)、TNX、富组氨酸糖蛋白(HRG)、高尔基相关蛋白1B(GAK1B)和胰岛素样生长因子结合蛋白5(fbp5/IBP5)】在化疗后显示出明显的信号减少。此外，Reatcome/KEGG通路分析和PPI分析表明，这其中6个属于脑组织，这些生物标记物大多参与PI3K-Akt、PI3K-Akt-mTOR和其他重要的信号通路，据报道与PCNSL的发生和发展有关，并成为各种癌症和神经退行性疾病的治疗靶点。磷酸化蛋白SPP1、TRH、TNC、SEPP1、IBP5和TNX与神经系统疾病相关，其中SPP1是PCNSL筛查的生物标志物。该团队能够从治疗前和治疗后的100μL CSF样本中定量它们的事实，突显了EVTOP方法的强大和未来应用的巨大潜力。四、总结|讨论该研究介绍的EVTOP磁珠有希望用于处理大样本批次、有限样本材料和具有挑战性的生物样本的临床筛查和生物标记物发现。该研究展示了EVTOP用于使用微量生物流体进行EV磷酸化蛋白质组谱分析的优势，未来改进该方法可以扩展到含有其他翻译后修饰的EV多肽的富集化，例如糖基化、乙酰化和其他修饰。EVTOP由于其超高灵敏度和稳定性，可以作为一种临床程序来筛选或靶向循环EVs中的功能蛋白，用于疾病诊断。参考文献：Jie Sun, et al, Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids through Functionally Tunable Paramagnetic Separation, Angew. Chem. Int. Ed. 2023, e202305668DOI: 10.1002/anie.202305668https://doi.org/10.1002/anie.202305668

临床研究