miR-146b 通过抑制 FGL2 激活的 NF-κB/MAPK 信号通路抑制 LPS 诱导的 M1 巨噬细胞极化在炎症性肠病中。

miR-146b suppresses LPS-induced M1 macrophage polarization via inhibiting the FGL2-activated NF-κB/MAPK signaling pathway in inflammatory bowel disease.

机构信息

Department of Laboratory Medicine, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, China.

Digestive Department, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, China.

出版信息

Clinics (Sao Paulo). 2022 Jun 21;77:100069. doi: 10.1016/j.clinsp.2022.100069. eCollection 2022.

DOI:10.1016/j.clinsp.2022.100069

PMID:35749999

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9234609/

Abstract

OBJECTIVES

M1 macrophage polarization and phenotype in Inflammatory Bowel Disease (IBD) are common biological responses.

METHOD

Herein, IBD mice models were constructed and macrophages were derived.

RESULTS

It was discovered that microRNA-146b (miR-146b) was downregulated in IBD mice and Lipopolysaccharide (LPS)-induced macrophages. Moreover, the inhibitory role of overexpressed miR-146b in reducing the inflammation level and blocking M1 macrophage polarization was confirmed. Further investigation indicated that Fibrinogen Like 2 (FGL2) acted as the target gene of miR-146b, and FGL2 mediated activation of NLRP3, NF-κB-p65, and p38-MAPK. More importantly, it was validated that miR-146b could ameliorate inflammatory phenotype and prevent M1 macrophage polarization via inhibiting FGL2 in vitro, and miR-146b overexpression alleviated the intestinal injury of IBD mice in vivo.

CONCLUSIONS

Overall, it is potential to use miR-146b for the amelioration of IBD.

摘要

目的

M1 巨噬细胞极化和表型在炎症性肠病（IBD）中是常见的生物学反应。

方法

在此，构建了 IBD 小鼠模型并分离了巨噬细胞。

结果

发现微小 RNA-146b（miR-146b）在 IBD 小鼠和脂多糖（LPS）诱导的巨噬细胞中下调。此外，证实了过表达 miR-146b 在降低炎症水平和阻断 M1 巨噬细胞极化方面的抑制作用。进一步的研究表明，纤维蛋白原样蛋白 2（FGL2）是 miR-146b 的靶基因，并且 FGL2 介导 NLRP3、NF-κB-p65 和 p38-MAPK 的激活。更重要的是，验证了 miR-146b 可以通过抑制体外的 FGL2 来改善炎症表型和预防 M1 巨噬细胞极化，并且 miR-146b 过表达可以减轻体内 IBD 小鼠的肠道损伤。