PMID- 32641645
OWN - NLM
STAT- MEDLINE
DCOM- 20211112
LR  - 20211112
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Print)
IS  - 1340-3478 (Linking)
VI  - 28
IP  - 4
DP  - 2021 Apr 1
TI  - ALK7 Acts as a Positive Regulator of Macrophage Activation through 
      Down-Regulation of PPARgamma Expression.
PG  - 375-384
LID - 10.5551/jat.54445 [doi]
AB  - AIM: Activin receptor-like kinase 7 (ALK7) acts as a key receptor for TGF-beta 
      family members, which play important roles in regulating cardiovascular activity. 
      However, ALK7's potential role, and underlying mechanism, in the macrophage 
      activation involved in atherogenesis remain unexplored. METHODS: ALK7 expression 
      in macrophages was tested by RT-PCR, western blot, and immunofluorescence 
      co-staining. The loss-of-function strategy using AdshALK7 was performed for 
      functional study. Oil Red O staining was used to observe the foam cell formation, 
      while inflammatory mediators and genes related to cholesterol efflux and influx 
      were determined by RT-PCR and western blot. A PPARgamma inhibitor (G3335) was used to 
      reveal whether PPARgamma was required for ALK7 to affect macrophage activation. 
      RESULTS: The results exhibited upregulated ALK7 expression in oxidized 
      low-density lipoprotein (Ox-LDL) induced bone marrow derived macrophages (BMDMs) 
      and mouse peritoneal macrophages (MPMs), isolated from ApoE-deficient mice, while 
      ALK7's strong immunoreactivity in BMDMs was observed. ALK7 knockdown 
      significantly attenuated pro-inflammatory, but promoted anti-inflammatory, 
      macrophage markers expression. Additionally, ALK7 silencing decreased foam cell 
      formation, accompanied by the up-regulation of ABCA1 and ABCG1 involved in 
      cholesterol efflux but the down-regulation of CD36 and SR-A implicated in 
      cholesterol influx. Mechanistically, ALK7 knockdown upregulated PPARgamma expression, 
      which was required for the ameliorated effect of ALK7 silencing macrophage 
      activation. CONCLUSIONS: Our study demonstrated that ALK7 was a positive 
      regulator for macrophage activation, partially through down-regulation of PPARgamma 
      expression, which suggested that neutralizing ALK7 might be promising therapeutic 
      strategy for treating atherosclerosis.
FAU - Cheng, Wen-Lin
AU  - Cheng WL
AD  - Department of Cardiology, Zhongnan hospital, Wuhan University.
FAU - Zhang, Quan
AU  - Zhang Q
AD  - Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology.
FAU - Cao, Jian-Lei
AU  - Cao JL
AD  - Department of Cardiology, Zhongnan hospital, Wuhan University.
FAU - Chen, Xi-Lu
AU  - Chen XL
AD  - Department of Pediatric Surgery, Union Hospital,Tongji Medical College, Huazhong 
      University of Science and Technology.
FAU - Li, Wenyan
AU  - Li W
AD  - Department of Pharmacy, The First Hospital of Nanchang.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Department of Cardiology, Zhongnan hospital, Wuhan University.
FAU - Chao, Sheng-Ping
AU  - Chao SP
AD  - Department of Cardiology, Zhongnan hospital, Wuhan University.
FAU - Zhao, Fang
AU  - Zhao F
AD  - Department of Cardiology, Zhongnan hospital, Wuhan University.
LA  - eng
PT  - Journal Article
DEP - 20200709
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (ABCA1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (Apoe protein, mouse)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (PPAR gamma)
RN  - 0 (Pparg protein, mouse)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 2.7.11.30 (Activin Receptors, Type I)
RN  - EC 2.7.11.30 (Acvr1c protein, mouse)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/*metabolism
MH  - *Activin Receptors, Type I/antagonists & inhibitors/genetics/metabolism
MH  - Animals
MH  - Apolipoproteins E/metabolism
MH  - *Atherosclerosis/drug therapy/metabolism
MH  - Cells, Cultured
MH  - Drug Discovery
MH  - Lipoproteins, LDL/metabolism
MH  - Macrophage Activation/*physiology
MH  - Macrophages/*metabolism
MH  - Macrophages, Peritoneal/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - *PPAR gamma/antagonists & inhibitors/metabolism
MH  - Up-Regulation
PMC - PMC8147563
OTO - NOTNLM
OT  - ALK7
OT  - Atherosclerosis
OT  - Macrophage
OT  - PPARgamma
COIS- None.
EDAT- 2020/07/10 06:00
MHDA- 2021/11/16 06:00
PMCR- 2021/04/01
CRDT- 2020/07/10 06:00
PHST- 2020/07/10 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2020/07/10 06:00 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - 10.5551/jat.54445 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2021 Apr 1;28(4):375-384. doi: 10.5551/jat.54445. Epub 2020 
      Jul 9.