Negative feedback loop of ERK/CREB/miR‐212‐3p inhibits HBeAg‐induced macrophage activation

Autor: Xiaoyu Xie, Xia Yang, Jianni Qi, Hongjun Bian, Yuejuan Zhang, Wenjun Chen, Benjun Bi, Jing Song, Chunliu Li, Qiang Zhu, Chengyong Qin
Rok vydání: 2020
Předmět:
0301 basic medicine
MAPK/ERK pathway
Chromatin Immunoprecipitation
MAP Kinase Signaling System
THP-1 Cells
medicine.medical_treatment
p38 mitogen-activated protein kinases
macrophage
HBeAg
CREB
Monocytes
miR‐212‐3p
MAPK1
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
Macrophage
Hepatitis B e Antigens
Cyclic AMP Response Element-Binding Protein
Promoter Regions
Genetic
Transcription factor
Feedback
Physiological
Inflammation
Gene knockdown
biology
Chemistry
virus diseases
Original Articles
U937 Cells
Cell Biology
Macrophage Activation
digestive system diseases
Cell biology
MicroRNAs
RAW 264.7 Cells
030104 developmental biology
Cytokine
Gene Expression Regulation
030220 oncology & carcinogenesis
biology.protein
Cytokines
Molecular Medicine
Original Article
Protein Binding
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
Popis: The activation of liver macrophages is closely related to liver injury after HBV infection. Our previous results demonstrated that HBeAg played a key role in inducing macrophage activation. As we all know, miRNAs are involved in the regulation of multiple immune cell functions. Meanwhile, we have shown that miR‐155 positively regulates HBeAg‐induced macrophage activation and accelerates liver injury. Subsequently, based on our previous miRNA sequencing results, we further evaluated the role of miR‐212‐3p called ‘neurimmiR’ in HBeAg‐induced macrophages in this study. First, miR‐212‐3p expression was significantly elevated in HBeAg‐treated macrophages. Meanwhile, we found up‐regulation of miR‐212‐3p significantly decreased the production of cytokines, whereas knockdown of miR‐212‐3p held the opposite effect by gains and losses of function. Mechanically, although MAPK signal pathway, including ERK, JNK and p38, was activated in HBeAg‐induced macrophages, only ERK promoted the expression of miR‐212‐3p via transcription factor CREB, which was able to bind to the promoter of miR‐212‐3p verified by ChIP assay. Moreover, we further indicated that up‐regulated miR‐212‐3p inhibited HBeAg‐induced inflammatory cytokine production through targeting MAPK1. In conclusion, miR‐212‐3p was augmented in HBeAg‐stimulated macrophages via ERK/CREB signal pathway and the elevated miR‐212‐3p suppressed inflammatory cytokine production induced by HBeAg through targeting MAPK1.
Databáze: OpenAIRE
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