Ablation of Galectin-12 Inhibits Atherosclerosis through Enhancement of M2 Macrophage Polarization

被引：12

作者：

Lin, En-Shyh ^{[1
]}

Hsu, Yu-An ^{[2
]}

Chang, Ching-Yao ^{[3
]}

Lin, Hui-Ju ^{[2
,4
]}

Chen, Chih Sheng ^{[5
,6
,7
]}

Wan, Lei ^{[2
,3
,8
]}

机构：

[1] Natl Taichung Univ Sci & Technol, Dept Beauty Sci, Taichung 403, Taiwan

[2] China Med Univ, Sch Chinese Med, Taichung 404, Taiwan

[3] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan

[4] China Med Univ Hosp, Dept Ophthalmol, Taichung 404, Taiwan

[5] Asia Univ Hosp, Div Chinese Med, Taichung 413, Taiwan

[6] Asia Univ, Dept Food Nutr & Hlth Biotechnol, Taichung 413, Taiwan

[7] China Med Univ Hosp, Dept Chinese Med, Taichung 404, Taiwan

[8] China Med Univ Hosp, Dept Obstet & Gynecol, Taichung 404, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 15期

关键词：

atherosclerosis; foam cell; galectin-12; low-density lipoprotein; macrophage polarization; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHOLESTEROL EFFLUX; INSULIN SENSITIVITY; EXPRESSION; INFLAMMATION; CELLS;

D O I：

10.3390/ijms21155511

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The formation of foam cells, which are macrophages that have engulfed oxidized low-density lipoprotein (OxLDL), constitutes the first stage in the development of atherosclerosis. Previously, we found that knocking down galectin-12, a negative regulator of lipolysis, leads to reduced secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that plays an important role in atherosclerosis. This prompted us to study the role of galectin-12 in atherosclerosis. With that aim, we examined foam cell formation in Gal12(-/-)murine macrophages exposed to OxLDL and acetylated LDL (AcLDL). Then, we generated an LDL receptor and galectin-12 double knockout (DKO) mice and studied the effect of galectin-12 on macrophage function and atherosclerosis. Lastly, we evaluated the role of galectin-12 in human THP-1 macrophages using a doxycycline-inducible conditional knockdown system. Galectin-12 knockout significantly inhibited foam cell formation in murine macrophages through the downregulation of cluster of differentiation 36 (CD36), and the upregulation of ATP Binding Cassette Subfamily A Member 1 (ABCA1), ATP Binding Cassette Subfamily G Member 1 (ABCG1), and scavenger receptor class B type 1 (SRB1). Consistent with this, galectin-12 knockdown inhibited foam cell formation in human macrophages. In addition, the ablation of galectin-12 promoted M2 macrophage polarization in human and murine macrophages as evidenced by the upregulation of the M2 marker genes,CD206andCD163,and downregulation of the M1 cytokines, tumor necrosis factor alpha (TNF- alpha), interleukin-6 (IL-6), and MCP-1. Moreover, the ablation of galectin-12 decreased atherosclerosis formation in DKO mice. Based on these results, we propose galectin-12 as a potential therapeutic target for atherosclerosis.

引用

页码：1 / 14

页数：14

共 35 条

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