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MiR-30b-5p Releases HMGB1 Via UBE2D2/KAT2B/HMGB1 Pathway to Promote Pro-inflammatory Polarization and Recruitment of Macrophages

Overview
Journal Atherosclerosis
Publisher Elsevier
Date 2021 Apr 3
PMID 33812169
Citations 9
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Abstract

Background And Aims: Oxidized low-density lipoprotein (ox-LDL) is a key risk factor for atherosclerosis, but there are few reports on ox-LDL-mediated inflammation after injury. In this study, we investigated the effects of ox-LDL on endothelial injury and macrophage polarization and recruitment using human aortic endothelial cell line HAEC cells.

Methods: Changes in miRNA levels after ox-LDL treatment were assessed with qRT-PCR. Luciferase experiments were performed to verify the interaction between miRNA and protein, and co-IP and ubiquitination experiments to detect proteins interactions. Cell phenotype was assessed by cytometry and Western blot.

Results: qRT-PCR data indicated that ox-LDL treatment up-regulates the expression of miR-30b-5p. Luciferase test and ubiquitination assay showed miR-30b-5p can bind to UBE2D2 and reduce its ubiquitination ability to degrade KAT2B. The up-regulated KAT2B promotes the acetylation of HMGB1, acetylated HMGB1 dissociates from SIRT1, exit the nucleus, and it is secreted from the cell. Flow cytometry and transwell experiments showed that HMGB1 secreted from HAEC can induce pro-inflammatory (M1-like) polarization and recruitment of RAW264.7 cells.

Conclusions: Our results indicate that ox-LDL activates the UBE2D2/KAT2B pathway by upregulating miR-30b-5p, thus acetylating HMGB1, which is then secreted from the cell, thereby promoting pro-inflammatory cell polarization and recruitment of macrophage.

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