Both HuR and miR-29s regulate expression of CB1 involved in infiltration of bone marrow monocyte/macrophage in chronic liver injury
Both HuR and miR-29s regulate expression of CB1 involved in infiltration of bone marrow monocyte/macrophage in chronic liver injury
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HuR和miR-29s均调节CB1的表达，参与慢性肝损伤中骨髓单核细胞/巨噬细胞的浸润
DOI：
10.1002/jcp.29157
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发表时间：
2019-09-08
影响因子：
5.6
通讯作者：
Li, Liying
中科院分区：
文献类型：
--
作者：
Chang, Na;Duan, Xianghui;Li, Liying
骨髓源性单核细胞/巨噬细胞 (BMM) 在肝脏炎症和纤维形成中发挥着至关重要的作用。大麻素受体 1 (CB1) 介导 BMM 募集到受损肝脏中。在这项研究中，我们揭示了CB1介导的BMM浸润的分子机制。使用四氯化碳（CCl4）诱导小鼠肝损伤。在体内，人类抗原 R (HuR) 在受损肝脏的巨噬细胞中表达上调。 HuR 信使 RNA (mRNA) 表达与 CB1 和 F4/80 mRNA 表达呈正相关。此外，我们在 CCl4 处理的肝脏中检测到 HuR 和 CB1 mRNA 之间的结合。在体外，HuR 通过调节 CB1 表达来调节花生四烯酰-2'-氯乙酰胺（ACEA，CB1 激动剂）诱导的 BMM 迁移。 HuR 通过与 CB1 mRNA 结合促进 CB1 表达。 ACEA 通过诱导 HuR 核质转运促进 HuR 和 CB1 mRNA 之间的关联。在细胞质中，HuR 与 miR-29 家族竞争以改善 CB1 表达和 BMM 迁移。总之，我们的结果证明 HuR 通过与 miR-29 家族竞争来调节 CB1 表达并影响 ACEA 诱导的 BMM 迁移。
Bone marrow-derived monocytes/macrophages (BMMs) play a vital role in liver inflammation and fibrogenesis. Cannabinoid receptor 1 (CB1) mediates the recruitment of BMMs into the injured liver. In this study, we revealed the molecular mechanisms under CB1-mediated BMM infiltration. Carbon tetrachloride (CCl4) was employed to induce mouse liver injury. In vivo, human antigen R (HuR) was upregulated in macrophages of injured liver. HuR messenger RNA (mRNA) expression was positively correlated with CB1 and F4/80 mRNA expression. Furthermore, we detected the binding between HuR and CB1 mRNA in CCl4-treated livers. In vitro, HuR modulated arachidonyl-2 '-chloroethylamide (ACEA, CB1 agonist)-induced BMM migration by regulating CB1 expression. HuR promoted CB1 expression via binding to CB1 mRNA. ACEA promoted the association between HuR and CB1 mRNA via inducing HuR nucleoplasmic transport. In the cytoplasm, HuR competed with the miR-29 family to improve CB1 expression and BMM migration. In conclusion, our results prove that HuR regulates CB1 expression and influences ACEA-induced BMM migration by competing with miR-29 family.