更新于：2024-11-01

COL4A1

更新于：2024-11-01

基本信息

别名

Arresten、COL4A1、Collagen alpha-1(IV) chain

+ [1]

简介

Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation.

关联

项与 COL4A1 相关的药物

CN116574180

专利挖掘

靶点

COL4A1

作用机制-

在研机构

南京金斯瑞生物科技有限公司

原研机构

南京金斯瑞生物科技有限公司

在研适应症

骨髓疾病 [+1]

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

100 项与 COL4A1 相关的临床结果

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100 项与 COL4A1 相关的转化医学

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0 项与 COL4A1 相关的专利（医药）

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990

项与 COL4A1 相关的文献（医药）

2024-11-01·American Journal of Medical Genetics Part A

COL4A1‐related disorder as a mimic of congenital TORCHES infection—Expanding the clinical, neuroimaging and genotype spectrum

Article

作者: Kukulka, Natalie A. ; Glass, Joshua ; Schroder, Jason ; Zarei, Sanam ; Bouska, Cecilia ; Sen, Kuntal

AbstractPseudo‐TORCH Syndrome (PTS) encompasses a heterogeneous group of genetic disorders that may clinically and radiologically resemble congenital TORCH infections. These mimickers present with overlapping features manifested as intracranial and systemic abnormalities. Collagen type IV alpha 1 chain (COL4A1)‐related diseases, characterized by autosomal dominant inheritance, exhibit a diverse phenotypic spectrum involving cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. Cerebrovascular manifestations range from small‐vessel brain disease to large vessel abnormalities, resulting in intracerebral hemorrhage, periventricular leukoencephalopathy, and ventriculomegaly. Additional features include cortical malformations, eye defects, arrhythmias, renal disease, muscular abnormalities, and hematological manifestations. Age of onset varies widely, and phenotypic variability exists even among individuals with the same variant. In this study, we present two cases of COL4A1‐related disorder mimicking congenital TORCH infections, highlighting the importance of recognizing genetic mimics in clinical practice.

2024-11-01·Experimental Eye Research

Influence of dexamethasone-induced matrices on the TM transcriptome

Article

作者: Raghunathan, Vijaykrishna ; Vranka, Janice A. ; Dhamodaran, Kamesh ; Baidouri, Hasna ; Yu, Hongfang ; Liu, Yutao ; Vranka, Janice A ; Xu, Hongyan ; Soundappan, Keerti ; Cai, Jingwen

Pathologic bidirectional interactions between the extracellular matrix (ECM) and cells within the human trabecular meshwork (hTM) contribute to ocular hypertension. An in vitro model is needed to study these cell-matrix interactions and their effect on outflow homeostasis. This study aimed to determine whether pathogenic ECM derived from dexamethasone (DEX)-treated hTM cultures induces clinically relevant glaucoma-like changes in healthy hTM cells at the transcriptional level. Corneoscleral rims from non-glaucoma donors were used to isolate primary hTM cells after validation according to the consensus recommendations for TM culture. Normal hTM cells (n = 5) were plated on a coverslip and treated with 100 nM DEX or ethanol for four weeks. These cultures were then decellularized, plated with primary hTM cells, and allowed to grow for another 72 h. RNA was extracted from these hTM cells for stranded total RNA-Seq. Sequencing libraries prepared using the Zymo-Seq RiboFree Total RNA library kit were pooled and sequenced using Illumina NovaSeq 6000. After quality control, sequence reads were aligned to the human genome build hg19. Differential expression (DE) analyses were performed using paired multi-factorial ANOVA. The expression of several DE genes associated with glaucoma (ANGPTL2, PDE7B, C22orf23, COL4A1, ADAM12, IFT122, SEMA6C) was validated using EvaGreen-based Droplet Digital PCR (ddPCR) assays. Gene ontology analyses of the DE genes were performed using the PANTHER and NDEx IQA databases, and functional analyses were performed with the DAVID Bioinformatics software. Using a cutoff of p-value <0.05 and fold change ≥2.0, our differential analysis identified 267 up- and 135 down-regulated genes in DEX-induced ECM-treated cells compared to the control. These differentially expressed genes were found to play a significant role in pathways such as cytokine and oxidative stress-induced inflammation, integrin signaling, matrix remodeling, and angiogenesis. These findings were further supported by previously performed proteomics studies using the same model. Using ddPCR, we validated the expression of seven genes associated with the risk of primary open-angle glaucoma. These results not only provide support for the pathogenic ECM model of steroid-induced glaucoma, but also demonstrate that the pathologic changes induced by this model are indeed found at the transcriptional level. These findings further demonstrate that matrix changes significantly influence cell expression profiles, which enable further understanding of the molecular mechanisms underlying glaucomatous changes in the TM. However, future studies with a larger and more diverse set of samples and longer time points are needed to confirm the utility of this model for mechanistic studies.

2024-11-01·Current Eye Research

Downregulation of LOX Overexpression Promotes Retinal Ganglion Cells Survival in an Acute Ocular Hypertension Model

Article

作者: Deng, Chengmin ; Zhu, Xiaoyan ; He, Dengling ; Yang, Man ; Jiang, Bingcai ; Chang, Yun

PURPOSETo investigate the effect of reducing Lysyl oxidase (LOX) overexpression on retinal ganglion cells (RGCs) apoptosis in an acute ocular hypertension (AOH) rat model.METHODSAOH rat model was performed by anterior chamber perfusion and either received an intravitreal injection with β-aminopropionitrile (BAPN) or normal saline. After 2wk, Quantification of survival RGCs in the retina was performed using Retrograde FluoroGold labeling. The mRNA expression levels of LOX, LOXL1-4, collagen 1a1 (Col1a1), collagen 3a1 (Col3a1), collagen4a1 (Col4a1), elastin (Eln), fibronectin1 (Fbn1), fibronectin4 (Fbn4) were determined by RT-qPCR. LOX expression was determined by Western blot (WB) analysis and immunohistochemistry. The RNA expression of LOX, Eln and Col1a1 in RGCs retrograde-labeled with 1,1'-dioctadecyl-3,3,3',3' tetra-methylindocarbocyanine perchlorate(DiI)that selected through FACS sorting were determined by RT-qPCR analysis. Changes of the retinal function were detected by Electroretinogram (ERG) analysis.RESULTSResults showed that significant LOX overexpression and loss of RGCs related to IOP exposure in AOH retinas. PCR analysis indicated significant increased mRNA level of Col1a1, Col3al and Eln in AOH retinas. Significant increase mRNA expression of LOX, Col1a1 and Eln in the RGCs were observed in AOH group compared with CON group. AOH rats injected with BAPN showed a significant decrease in LOX expression, reduced the loss of RGCs and retinal function damage.CONCLUSIONSThe results demonstrated that changes of LOX and specific ECM components in retina were correlated with AOH. Findings from this study indicated that preventing LOX over-expression may be protective against RGCs loss and retinal function damage in AOH animal model.

项与 COL4A1 相关的新闻（医药）

2023-02-28

·生物谷

科学家开发了诊断子宫颈癌和治疗免疫抑制的肿瘤微环境的新方法

宫颈癌(CC)是妇科第三大常见癌症和第四大致死原因，但其确切进展尚不明确，主要是由于肿瘤发生的不同阶段肿瘤微环境变化的高度复杂性所致。宫颈癌(CC)是妇科第三大常见癌症和第四大致死原因，但其确切进展尚不明确，主要是由于肿瘤发生的不同阶段肿瘤微环境变化的高度复杂性所致。重要的是，缺乏对CC患者不同阶段肿瘤微环境(TME)的详细比较单核转录分析。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1186/s13046-023-02598-0 近日，来自佛山市第一人民医院的研究者们在J Exp Clin Cancer Res杂志上发表了题为“Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer”的文章，该研究为破译CC的进展提供了重要的资源，并为开发诊断CC和治疗免疫抑制的TME的新方法奠定了基础。在这项研究中，从I期和II期CC患者的肿瘤组织中提取了42,928和29,200个核，并进行了单核RNA测序(SnRNA-seq)分析。利用生物信息学工具对细胞异质性和功能进行比较研究。此外，还进行了基于无标记定量质谱学的蛋白质组学分析。比较I期和II期CC患者的蛋白质组图谱，并与SnRNA-seq进行整合分析。与I期CC(CCI)患者相比，II期CC(CCII)患者多种免疫细胞中与免疫反应相关的信号通路受到抑制，但与细胞和组织发育相关的信号丰富，线粒体相关基因上调提示代谢产生能量。这与定量蛋白质组学分析显示CCII组TME中促进细胞生长和细胞间基质发育的蛋白质占主导地位是一致的。在脑梗塞患者的许多细胞群体中，干扰素-α和γ反应出现了最活跃的通路。在CCII组中发现COL12A1、COL5A1、COL4A1和COL4A2等几种胶原蛋白显著上调，提示它们在诊断CC进展中的作用。一个新的转录本AC244205.1被检测到是CCII患者中最上调的基因，其在CC中的可能机制可能被进一步研究。 CCI患者TME中肿瘤相关干细胞(TASCs)和上皮细胞的免疫反应更为活跃图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1186/s13046-023-02598-0 在这项研究中，我们用SnRNA-seq和无标记定量蛋白质组学方法比较研究了I期和II期CC患者的TME。结果表明，II期CC患者几乎所有免疫细胞，包括MΦs、T细胞、B细胞、NK细胞和树突状细胞的异质性受到很大程度的调节，其表型具有明显的免疫抑制作用。相比之下，这些细胞在I期CC患者中表现出高免疫反应，其中干扰素-α和γ反应是最活跃的信号通路。几个组蛋白显示了在早期诊断CC的潜力。值得注意的是，对于II期CC患者，多种细胞类型的SnRNA-seq分析和蛋白质组分析分别鉴定出胶原蛋白的显著上调，提示它们可能作为预后标志物。首次揭示了新转录本AC244205.1的异常表达与II期CC的相关性。这些发现为CC的临床诊断和免疫治疗提供了重要线索，值得进一步研究。（生物谷 Bioon.com）参考文献 Xiaosong Liu et al. Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer. J Exp Clin Cancer Res. 2023 Jan 23;42(1):28. doi: 10.1186/s13046-023-02598-0.