期刊
MICROBIAL PATHOGENESIS
卷 167, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.micpath.2022.105564
关键词
Ror2; Cholesterol metabolism; Autophagy; Bacillus Calmette-Guerin; Macrophage
资金
- National Natural Science Foundation of China [31960700, 31960712]
This study aimed to explore the pathways that regulate Ror2-regulated cholesterol accumulation in macrophages and found that Ror2 can shape the autophagic activity in macrophages by modulating intracellular cholesterol levels.
Ror2 is a primary binding partner for the non-classical Wnt signaling pathway regulator Wnt5a that plays a central role in regulating the metabolic processing of lipids within the cell. Mycobacterium tuberculosis is an intracellular pathogen that utilizes the lipid substrate cholesterol as its primary source of carbon. Cholesterol accumulation can regulate autophagy, which is in turn associated with a variety of pathological conditions. This study was designed to explore the pathways that modulate Ror2-regulated cholesterol accumulation within macrophages infected by the mycobacterium Bacillus Calmette-Guerin (BCG). BCG infection of RAW264.7 cells resulted in increased Ror2 expression, cholesterol accumulation, and autophagic activity in addition to promoting the upregulation of cholesterol synthesis-related proteins and the downregulation of cholesterol transporter proteins. Ror2 knockdown, in contrast, reversed these phenotypic changes. Treatment with T0901317 decreased the aggregation of cholesterol within cells and suppressed BCG-induced autophagy, while OX-LDL had the opposite effect. Knocking down Ror2 further reduced cholesterol levels in the context of T0901317 or OX-LDL pretreatment, alleviating BCG-induced autophagy irrespective of either of these pretreatments. Together, these data indicate that Ror2 can shape the autophagic activity induced within macrophages upon BCG infection by modulating intracellular cholesterol levels.
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