Circulating plasma derived exosomes from systemic lupus erythematosus aggravate lupus nephritis through miR-122-5p/FOXO3-mediated macrophage activation

Bibliographic Details
Title: Circulating plasma derived exosomes from systemic lupus erythematosus aggravate lupus nephritis through miR-122-5p/FOXO3-mediated macrophage activation
Authors: Juan Ji, Qian He, Yunfei Xia, Xiaoqi Sha, Qian Liang, Yongxin Xu, Pengyu Chen, Chen Dong, Rui Zhao, Junling Yang, Hua Guo, Yunan Wang, Haixia Cao, Jing Li, Mei Yang, Zhifeng Gu
Source: Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-16 (2024)
Publisher Information: BMC, 2024.
Publication Year: 2024
Collection: LCC:Biotechnology
LCC:Medical technology
Subject Terms: Systemic lupus erythematosus, Exosomes, miR-122-5p, Macrophages, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
More Details: Abstract Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease characterized by dysregulation in both innate and adaptive immunity. Polarization of macrophages into M1/M2 macrophages affects the development of lupus. Exosomes-miRNA plays a crucial role in disease progression. This study aims to explore the mechanism of circulating exosomes participating in the pathogenesis of SLE and seek new therapeutic targets. Plasma derived-exosomes from SLE patients accelerated the disease progression and polarization of macrophages of the kidney in MRL/lpr mice. Exosomes were taken up by macrophages and stimulated macrophage polarization in vitro. MiRNA-sequence analysis revealed that plasma-derived exosomal miR-151a-5p, miR-1180a-5p, miR-1246 and miR-122-5p were abnormal. Of them, the expression of miR-122-5p was significantly upregulated in SLE exosomes, and positively correlated with systemic lupus erythematosus disease activity index (SLEDAI) and the dsDNA levels. Compared with SLE exosomes, inhibition of circulating exosomal miR-122-5p from SLE patients relieved lupus clinical aspects and polarization of macrophage. SLE exosomal miR-122-5p motivated M1 macrophage polarization by targeting FOXO3/NF-κB signaling pathway. Based on these findings, we conclude that SLE exosomal miR-122-5p can promote M1 macrophage polarization via targeting FOXO3/NF-κB signaling pathway and participate in pathogenesis of SLE. Collectively, plasma-derived exosomal miR-122-5p is a promising and effective target for treating SLE. Graphical Abstract
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1477-3155
Relation: https://doaj.org/toc/1477-3155
DOI: 10.1186/s12951-024-03063-6
Access URL: https://doaj.org/article/17781de017174aa195d70561009fb582
Accession Number: edsdoj.17781de017174aa195d70561009fb582
Database: Directory of Open Access Journals
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More Details
ISSN:14773155
DOI:10.1186/s12951-024-03063-6
Published in:Journal of Nanobiotechnology
Language:English