RNA-Seq reveals placental growth factor regulates the human retinal endothelial cell barrier integrity by transforming growth factor (TGF-β) signaling.
RNA-Seq reveals placental growth factor regulates the human retinal endothelial cell barrier integrity by transforming growth factor (TGF-β) signaling.
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DOI：
10.1007/s11010-020-03862-z
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发表时间：
2020-12
影响因子：
4.3
通讯作者：
Fan L
中科院分区：
文献类型：
--
作者：
Huang H;Saddala MS;Lennikov A;Mukwaya A;Fan L
胎盘生长因子（PlGF 或 PGF）是 VEGF（血管内皮生长因子）家族的成员。它在炎症、血管通透性和病理性血管生成中发挥病理作用。 PlGF 在非增殖性糖尿病视网膜病变 (DR) 中介导其作用的分子信号传导仍然难以捉摸。本研究旨在表征 PlGF 信号存在和不存在时人视网膜内皮细胞 (HREC) 转录组的变化。用 PlGF 抗体 (ab) 处理原代 HREC 以阻断其活性。分离总 RNA 并进行深度测序，以量化两组的转录本及其变化。我们进行了全转录组分析、基因本体论、通路富集和基因-基因网络分析。结果显示，共有3760个基因存在显着差异表达，分为细胞粘附分子、细胞连接蛋白、分子伴侣、钙结合蛋白和膜运输蛋白。功能通路分析表明，TGF-β通路、磷酸戊糖通路和细胞粘附通路在血视网膜屏障（BRB）和抗氧化防御系统中发挥着关键作用。总的来说，这些数据为与 DR 和糖尿病性黄斑水肿 (DME) 相关的 HREC 中 PlGF 生物学功能的分子机制提供了新的见解。新发现的基因和通路可以作为疾病标志物和靶分子，用于治疗对当前抗 VEGF 疗法无效的 DR 和 DME 患者。
Placental growth factor (PlGF or PGF) is a member of the VEGF (vascular endothelial growth factor) family. It plays a pathological role in inflammation, vascular permeability, and pathological angiogenesis. The molecular signaling by which PlGF mediates its effects in nonproliferative diabetic retinopathy (DR) remains elusive. This study aims to characterize the transcriptome changes of human retinal endothelial cells (HRECs) with the presence and the absence of PlGF signaling. Primary HRECs were treated with the PlGF antibody (ab) to block its activity. The total RNA was isolated and subjected to deep sequencing to quantify the transcripts and their changes in both groups. We performed transcriptome-wide analysis, gene ontology, pathway enrichment, and gene-gene network analyses. The results showed that a total of 3760 genes were significantly differentially expressed and were categorized into cell adhesion molecules, cell junction proteins, chaperone, calcium-binding proteins, and membrane traffic proteins. Functional pathway analyses revealed that the TGF-β pathway, pentose phosphate pathway, and cell adhesion pathway play pivotal roles in the blood-retina barrier (BRB) and antioxidant defense system. Collectively, the data provide new insights into the molecular mechanisms of PlGF’s biological functions in HRECs relevant to DR and diabetic macular edema (DME). The newly identified genes and pathways may act as disease markers and target molecules for therapeutic interventions for the patients with DR and DME refractory to the current anti-VEGF therapy.
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影响因子：
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作者：
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通讯作者：
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