PMID- 32752134
OWN - NLM
STAT- MEDLINE
DCOM- 20210222
LR  - 20210222
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 15
DP  - 2020 Jul 31
TI  - Ablation of Galectin-12 Inhibits Atherosclerosis through Enhancement of M2 
      Macrophage Polarization.
LID - 10.3390/ijms21155511 [doi]
LID - 5511
AB  - 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, CD206 and CD163, 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.
FAU - Lin, En-Shyh
AU  - Lin ES
AD  - Department of Beauty Science, National Taichung University of Science and 
      Technology, Taichung 403, Taiwan.
FAU - Hsu, Yu-An
AU  - Hsu YA
AD  - School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
FAU - Chang, Ching-Yao
AU  - Chang CY
AD  - Department of Biotechnology, Asia University, Taichung 413, Taiwan.
FAU - Lin, Hui-Ju
AU  - Lin HJ
AD  - School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
AD  - Department of Ophthalmology, China Medical University Hospital, Taichung 404, 
      Taiwan.
FAU - Chen, Chih Sheng
AU  - Chen CS
AD  - Division of Chinese Medicine, Asia University Hospital, Taichung 413, Taiwan.
AD  - Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 
      413, Taiwan.
AD  - Department of Chinese Medicine, China Medicine University Hospital, Taichung 404, 
      Taiwan.
FAU - Wan, Lei
AU  - Wan L
AUID- ORCID: 0000-0002-9525-3232
AD  - School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
AD  - Department of Biotechnology, Asia University, Taichung 413, Taiwan.
AD  - Department of Obstetrics and Gynecology, China Medical University Hospital, 
      Taichung 404, Taiwan.
LA  - eng
GR  - MOST107-2320-B-039-049-MY3/Ministry of Science and Technology, Taiwan/
GR  - CMU108-MF-40/China Medical University, Taiwan/
GR  - CMU108-ASIA-05/China Medical University, Taiwan/
PT  - Journal Article
DEP - 20200731
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (CD36 Antigens)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Galectins)
RN  - 0 (Lgals12 protein, mouse)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptors, LDL)
RN  - 0 (Scarb1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 0 (oxidized low density lipoprotein)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/genetics
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics
MH  - Animals
MH  - Atherosclerosis/*genetics/metabolism/pathology
MH  - CD36 Antigens/genetics
MH  - Cell Cycle Proteins/*genetics
MH  - Cell Polarity/genetics
MH  - Disease Models, Animal
MH  - Foam Cells/metabolism/pathology
MH  - Galectins/*genetics
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Lipoproteins, LDL/genetics/metabolism
MH  - Macrophages/*metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, LDL/*genetics
MH  - Scavenger Receptors, Class B/genetics
PMC - PMC7432701
OTO - NOTNLM
OT  - atherosclerosis
OT  - foam cell
OT  - galectin-12
OT  - low-density lipoprotein
OT  - macrophage polarization
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2020/08/06 06:00
MHDA- 2021/02/23 06:00
PMCR- 2020/08/01
CRDT- 2020/08/06 06:00
PHST- 2020/06/23 00:00 [received]
PHST- 2020/07/14 00:00 [revised]
PHST- 2020/07/17 00:00 [accepted]
PHST- 2020/08/06 06:00 [entrez]
PHST- 2020/08/06 06:00 [pubmed]
PHST- 2021/02/23 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - ijms21155511 [pii]
AID - ijms-21-05511 [pii]
AID - 10.3390/ijms21155511 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jul 31;21(15):5511. doi: 10.3390/ijms21155511.