Paxillin mediates endothelial cell migration and angiogenesis following spinal cord injury: a transcriptomic and functional analysis.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Manjeet Chopra, Jaidev Sharma, Aditya A Singh, Zarna Pathak, Priyanka Patel Vats, Vibhor Kumar, Amit Mandoli, Hemant Kumar
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引用次数: 0

Abstract

Spinal cord injury (SCI) is a destructive neurological condition that leads to significant functional deficits in the affected individual. To map the altered pathways within the lesion epicentre and the surrounding rostrocaudal segments, we performed RNA-sequencing on injured spinal cord tissue. Samples were collected from three regions-rostral, epicentre, and caudal-at Days 1, 14, and 28 post-injury to systematically profile the transcriptomic changes and identify pathways associated with angiogenesis following SCI. Gene set enrichment analysis revealed enriched pathways, including hepatocyte growth factor (HGF) receptor and alpha 6 beta 4 integrin signalling, indicating an active angiogenic response. The involvement of HGF receptor signalling was further validated by quantitative polymerase chain reaction (qPCR), confirming its role in pathological remodelling after SCI. Subsequently, we identified paxillin (Pxn) as a candidate gene that promotes endothelial cell migration via HGF receptor signalling. Immunohistochemistry demonstrated the role of Pxn in mediating endothelial cell migration and proliferation post-SCI. In summary, our findings indicate that Pxn is a key mediator of endothelial cell proliferation and migration in response to angiogenic factors, such as HGF, following SCI. However, further mechanistic studies are required to fully establish the role of Pxn in endothelial cell migration and proliferation after SCI.

帕罗西林介导脊髓损伤后内皮细胞迁移和血管生成:转录组学和功能分析。
脊髓损伤(SCI)是一种破坏性的神经系统疾病,在受影响的个体中导致显著的功能缺陷。为了绘制病变震中和周围背侧节段内改变的通路,我们对受损脊髓组织进行了rna测序。在损伤后的第1、14和28天,从吻侧、震中和尾侧三个区域收集样本,系统地分析脊髓损伤后的转录组变化,并确定与血管生成相关的途径。基因集富集分析显示,肝细胞生长因子(HGF)受体和α 6 β 4整合素信号通路富集,表明血管生成反应活跃。定量聚合酶链反应(qPCR)进一步证实了HGF受体信号的参与,证实了其在脊髓损伤后病理重塑中的作用。随后,我们确定了paxillin (Pxn)作为通过HGF受体信号传导促进内皮细胞迁移的候选基因。免疫组化证实Pxn在脊髓损伤后介导内皮细胞迁移和增殖中的作用。综上所述,我们的研究结果表明,在脊髓损伤后血管生成因子(如HGF)的作用下,Pxn是内皮细胞增殖和迁移的关键介质。然而,为了充分确定Pxn在脊髓损伤后内皮细胞迁移和增殖中的作用,还需要进一步的机制研究。
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来源期刊
Molecular omics
Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
5.40
自引率
3.40%
发文量
91
期刊介绍: Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.
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