miR-155 activates the NLRP3 inflammasome by regulating the MEK/ERK/NF-κB pathway in carotid atherosclerotic plaques in ApoE−/− mice
miR-155 activates the NLRP3 inflammasome by regulating the MEK/ERK/NF-κB pathway in carotid atherosclerotic plaques in ApoE−/− mice
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miR-155通过调节MEK/ERK/NF-κB通路激活ApoE−/−小鼠颈动脉粥样硬化斑块中的NLRP 3炎性体
DOI：
10.1007/s13105-022-00871-y
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Qing Peng;R. Yin;Xiaoyan Zhu;Liying Jin;Jing Wang;Xudong Pan;Aijun Ma
中科院分区：
文献类型：
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作者：
Qing Peng;R. Yin;Xiaoyan Zhu;Liying Jin;Jing Wang;Xudong Pan;Aijun Ma
动脉粥样硬化是一种炎症性疾病。NLRP 3炎性体和miR-155是炎症和动脉粥样硬化的重要组成部分。本研究旨在探讨miR-155通过NLRP 3炎性体介导颈动脉粥样硬化斑块形成的可能机制。将50只6周龄雄性ApoE−/−小鼠随机分为5组。分别为空白组、阴性对照组、miR-155模拟物组、miR-155抑制剂组、miR-155模拟物+ERK抑制剂组。采用酶法、油红O法、HE染色法测定血脂水平，免疫组化染色观察颈动脉斑块形成程度。采用PCR检测miR-155的表达。血脂测定采用酶法。Western blotting检测NLRP 3炎性小体相关蛋白、IL-1β、IL-18和MEK/ERK/NF-κB信号通路相关蛋白的表达。与NC组相比，miR-155模拟物组的miR-155表达显著增加（P< 0.05），颈动脉斑块形成程度增加，血浆TC、LDL水平也明显升高（P< 0.05）; NLRP 3炎性小体相关蛋白、白细胞介素-1 β、白细胞介素-18 MEK/ERK/NF-κB信号通路相关蛋白表达也显著增加。向miR-155模拟小鼠注射ERK抑制剂可降低p-NF-κB、NLRP 3炎性小体相关蛋白和炎性细胞因子的表达水平。综上所述，miR-155可以促进ApoE−/−小鼠动脉粥样硬化斑块的形成，这可能是通过调节MEK/ERK/NF-κB通路激活NLRP 3炎性体实现的。亮点·在ApoE−/−小鼠中，miR-155促进动脉粥样硬化斑块的形成。·NLRP 3炎性体在动脉粥样硬化的炎症过程中起重要作用。miR-155通过调节ApoE−/−小鼠颈动脉粥样硬化斑块中的MEK/ERK/NF-κB通路激活NLRP 3炎性体。
Atherosclerosis is an inflammatory disease. The NLRP3 inflammasome and miR-155 are significant components of inflammation and atherosclerosis. The aim of this research was to explore the possible mechanism by which miR-155 mediates the formation of carotid atherosclerotic plaques via the NLRP3 inflammasome. Fifty 6-week-old male ApoE−/−mice were randomly divided into 5 groups. They are the blank group, the negative control (NC) group, the miR-155 mimic group, the miR-155 inhibitor group, and the miR-155 mimic and ERK inhibitor group. The blood lipid levels were measured by the enzyme method Oil red O, HE, and immunohistochemical staining were used to observe the degree of carotid plaque formation. PCR was used to measure the expression of miR-155. The blood lipid levels were measured by the enzyme method. Western blotting was used to measure the expression of NLRP3 inflammasome-related proteins, interleukin-1β, interleukin-18, and MEK/ERK/NF-κB signaling pathway-related proteins. Compared with those of the NC group, the expression of miR-155 in the miR-155 mimic group increased significantly (P< 0.05), the degree of carotid plaque formation increased, the plasma levels of TC and LDL also increased significantly (P< 0.05); the expression levels of NLRP3 inflammasome-related proteins, interleukin-1β, interleukin-18, and MEK/ERK/NF-κB signaling pathway-related proteins were also significantly increased. Injection of ERK inhibitors into miR-155 mimic mice reduced the expression levels of p-NF-κB, NLRP3 inflammasome-related proteins, and inflammatory cytokines. In conclusion, miR-155 can promote the formation of atherosclerotic plaque in ApoE−/−mice, which may be achieved by regulating the MEK/ERK/NF-κB pathway to activate the NLRP3 inflammasome.Highlights• In ApoE−/−mice, miR-155 promotes atherosclerotic plaque formation.• The NLRP3 inflammasome has an important role in the inflammatory process of atherosclerosis.• miR-155 activates the NLRP3 inflammasome by regulating the MEK/ERK/NF-κB pathway in carotid atherosclerotic plaques of ApoE−/−mice.