Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Int J Mol Med. 2020 Jun;45(6):1735-1752. doi: 10.3892/ijmm.2020.4538. Epub 2020 Mar 13.
Krüppel‑like family (KLF) members are important regulators of proinflammatory activation in the vasculature. A transcriptome study involving RNA sequencing (RNA‑seq) and quantitative PCR (qPCR) was performed to investigate Klf15 and Klf15‑regulated gene levels in C57BL/6 mice with inferior vena cava thrombi and in control (Blank) mice. A total of 2,206 differentially expressed genes (DEGs), including 1,330 upregulated and 876 downregulated genes, were identified between the deep venous thrombosis (DVT) group and the Blank group. Additionally, 1,041 DEGs (235 upregulated and 806 downregulated) were identified between the Klf15‑small interfering RNA (siRNA) and Klf15‑negative control (NC) groups. The DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and qPCR was conducted to validate the results. A total of seven significant DEGs were selected from the RNA‑seq results. Matrix metalloproteinases (Mmp)12, Mmp13, Mmp19, Arg1, Ccl2, heme oxygenase‑1 and Fmo3 levels were significantly higher, while Klf15 levels were lower, in the DVT group than in the Blank group. Fmo3 and Mmp19 have not been previously identified as DVT‑associated DEGs. Klf15, Mmp12 and Mmp13 levels were compared between the Klf15‑siRNA and Klf15‑NC groups. Mmp12 and Mmp13 expression was significantly higher, while that of Klf15 was lower, in the Klf15‑siRNA group than in the Klf15‑NC group. Critical roles of Klf15, Mmp12 and Mmp13 have been identified, which have not previously been shown to help regulate DVT initiation and progression. Moreover, Klf15‑mediated regulation of DVT may be modulated by downregulation of various genes, such as Mmp12 and Mmp13, potentially providing a theoretical foundation and diagnostic criteria for DVT treatment.
Krüppel 样家族（KLF）成员是血管中促炎激活的重要调节因子。进行了一项涉及 RNA 测序（RNA-seq）和定量 PCR（qPCR）的转录组研究，以研究 C57BL/6 小鼠下腔静脉血栓形成和对照（Blank）小鼠中的 Klf15 和 Klf15 调节基因水平。在深静脉血栓形成（DVT）组和 Blank 组之间共鉴定出 2206 个差异表达基因（DEGs），包括 1330 个上调基因和 876 个下调基因。此外，在 Klf15-siRNA 和 Klf15-阴性对照（NC）组之间还鉴定出 1041 个 DEGs（235 个上调和 806 个下调）。对 DEGs 进行了基因本体论和京都基因与基因组百科全书富集分析，并进行了 qPCR 验证。从 RNA-seq 结果中选择了 7 个显著的 DEGs。Mmp12、Mmp13、Mmp19、Arg1、Ccl2、血红素加氧酶-1 和 Fmo3 水平在 DVT 组中明显高于 Blank 组，而 Klf15 水平则低于 Blank 组。Fmo3 和 Mmp19 以前没有被确定为与 DVT 相关的 DEGs。比较了 Klf15-siRNA 和 Klf15-NC 组之间的 Klf15、Mmp12 和 Mmp13 水平。Mmp12 和 Mmp13 的表达在 Klf15-siRNA 组中明显高于 Klf15-NC 组，而 Klf15 的表达则低于 Klf15-NC 组。已经确定了 Klf15、Mmp12 和 Mmp13 的关键作用，这些作用以前没有被证明有助于调节 DVT 的起始和进展。此外，Klf15 介导的 DVT 调节可能通过下调各种基因如 Mmp12 和 Mmp13 来调节，这可能为 DVT 治疗提供理论基础和诊断标准。
