Silencing of long non-coding RNA H19 downregulates CTCF to protect against atherosclerosis by upregulating PKD1 expression in ApoE knockout mice
Silencing of long non-coding RNA H19 downregulates CTCF to protect against atherosclerosis by upregulating PKD1 expression in ApoE knockout mice
复制标题
在 ApoE 敲除小鼠中，长非编码 RNA H19 的沉默可下调 CTCF，从而通过上调 PKD1 表达来预防动脉粥样硬化
DOI：
10.18632/aging.102388
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发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Wu, Qiang
中科院分区：
文献类型：
--
作者：
Yang, Yongyao;Tang, Feng;Wu, Qiang
本研究旨在探讨长链非编码RNA H19、转录因子CCCTC结合因子（CTCF）和多囊肾病1（PKD 1）之间的相互作用，探讨其对动脉粥样硬化易损斑块形成和血管生成的潜在调控作用。我们在ApoE基因敲除小鼠中建立了动脉粥样硬化小鼠模型，随后采用功能获得和功能丧失方法。H19在动脉粥样硬化小鼠的主动脉组织中上调，但H19的沉默显著抑制动脉粥样硬化易损斑块形成和斑块内血管生成，伴随着MMP-2、VEGF和p53的表达下调和TIMP-1的表达上调。此外，在H19或CTCF过表达治疗的动脉粥样硬化小鼠的主动脉组织中发现了相反的结果。H19能够募集CTCF抑制PKD 1，从而促进动脉粥样硬化小鼠动脉粥样硬化易损斑块的形成和斑块内血管生成。本研究提供的证据表明，H19招募CTCF下调PKD 1的表达，从而促进易损斑块的形成和斑块内血管生成的小鼠动脉粥样硬化。
This study aimed to explore the interactions among long non-coding RNA H19, transcriptional factor CCCTC-binding factor (CTCF) and polycystic kidney disease 1 (PKD1), and to investigate its potentially regulatory effect on vulnerable plaque formation and angiogenesis of atherosclerosis. We established an atherosclerosis mouse model in ApoE knockout mice, followed by gain- and loss-of-function approaches. H19 was upregulated in aortic tissues of atherosclerosis mice, but silencing of H19 significantly inhibited atherosclerotic vulnerable plaque formation and intraplaque angiogenesis, accompanied by a downregulated expression of MMP-2, VEGF, and p53 and an upregulated expression of TIMP-1. Moreover, opposite results were found in the aortic tissues of atherosclerosis mice treated with H19 or CTCF overexpression. H19 was capable of recruiting CTCF to suppress PKD1, thus promoting atherosclerotic vulnerable plaque formation and intraplaque angiogenesis in atherosclerosis mice. The present study provides evidence that H19 recruits CTCF to downregulate the expression of PKD1, thereby promoting vulnerable plaque formation and intraplaque angiogenesis in mice with atherosclerosis.