PMID- 37731037
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240108
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 45
IP  - 1
DP  - 2024 Jan
TI  - Par3L, a polarity protein, promotes M1 macrophage polarization and aggravates 
      atherosclerosis in mice via p65 and ERK activation.
PG  - 112-124
LID - 10.1038/s41401-023-01161-z [doi]
AB  - Proinflammatory M1 macrophages are critical for the progression of 
      atherosclerosis. The Par3-like protein (Par3L) is a homolog of the Par3 family 
      involved in cell polarity establishment. Par3L has been shown to maintain the 
      stemness of mammary stem cells and promote the survival of colorectal cancer 
      cells. In this study, we investigated the roles of the polar protein Par3L in M1 
      macrophage polarization and atherosclerosis. To induce atherosclerosis, Apoe(-/-) 
      mice were fed with an atherosclerotic Western diet for 8 or 16 weeks. We showed 
      that Par3L expression was significantly increased in human and mouse 
      atherosclerotic plaques. In primary mouse macrophages, oxidized low-density 
      lipoprotein (oxLDL, 50 mug/mL) time-dependently increased Par3L expression. In 
      Apoe(-/-) mice, adenovirus-mediated Par3L overexpression aggravated 
      atherosclerotic plaque formation accompanied by increased M1 macrophages in 
      atherosclerotic plaques and bone marrow. In mouse bone marrow-derived macrophages 
      (BMDMs) or peritoneal macrophages (PMs), we revealed that Par3L overexpression 
      promoted LPS and IFNgamma-induced M1 macrophage polarization by activating p65 and 
      extracellular signal-regulated kinase (ERK) rather than p38 and JNK signaling. 
      Our results uncover a previously unidentified role for the polarity protein Par3L 
      in aggravating atherosclerosis and favoring M1 macrophage polarization, 
      suggesting that Par3L may serve as a potential therapeutic target for 
      atherosclerosis.
CI  - (c) 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia 
      Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
FAU - Huang, Yi-Min
AU  - Huang YM
AD  - Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key 
      Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou 
      Medical University, Guangzhou, 511436, China.
FAU - Wu, Yu-Sen
AU  - Wu YS
AD  - Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key 
      Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou 
      Medical University, Guangzhou, 511436, China.
FAU - Dang, Yuan-Ye
AU  - Dang YY
AD  - Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key 
      Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou 
      Medical University, Guangzhou, 511436, China.
FAU - Xu, Yi-Ming
AU  - Xu YM
AD  - School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China.
FAU - Ma, Kong-Yang
AU  - Ma KY
AD  - Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen 
      University, Shenzhen, 518107, China.
FAU - Dai, Xiao-Yan
AU  - Dai XY
AD  - Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key 
      Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou 
      Medical University, Guangzhou, 511436, China. xdai@gzhmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230920
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - 0 (Apolipoproteins E)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - *Plaque, Atherosclerotic/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *Atherosclerosis/metabolism
MH  - Macrophages/metabolism
MH  - Apolipoproteins E/metabolism
MH  - Macrophage Activation
MH  - Mice, Inbred C57BL
PMC - PMC10770347
OTO - NOTNLM
OT  - ERK
OT  - Par3L
OT  - aorta
OT  - atherosclerosis
OT  - macrophage polarization
OT  - p65
COIS- The authors declare no competing interests.
EDAT- 2023/09/21 06:42
MHDA- 2024/01/08 06:43
PMCR- 2025/01/01
CRDT- 2023/09/21 00:15
PHST- 2023/04/13 00:00 [received]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2025/01/01 00:00 [pmc-release]
PHST- 2024/01/08 06:43 [medline]
PHST- 2023/09/21 06:42 [pubmed]
PHST- 2023/09/21 00:15 [entrez]
AID - 10.1038/s41401-023-01161-z [pii]
AID - 1161 [pii]
AID - 10.1038/s41401-023-01161-z [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2024 Jan;45(1):112-124. doi: 10.1038/s41401-023-01161-z. Epub 
      2023 Sep 20.