PMID- 32065217
OWN - NLM
STAT- MEDLINE
DCOM- 20210325
LR  - 20211204
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 40
IP  - 3
DP  - 2020 Mar 27
TI  - ALK5 deficiency inhibits macrophage inflammation and lipid loading by targeting 
      KLF4.
LID - 10.1042/BSR20194188 [doi]
LID - BSR20194188
AB  - The transforming growth factor type-beta (TGF-beta) has been demonstrated to play an 
      important role in the development of atherosclerosis through binding to the 
      serine/threonine kinase transmembrane type I and type II receptors. However, as a 
      key type I receptor for TGF-beta, the exact role and the underlying mechanism of 
      Activin receptor-like kinase 5 (ALK5) on macrophage activation involved in 
      atherogenesis remain unclear. In the present study, enhanced ALK5 expression was 
      found in bone marrow derived macrophages (BMDMs) upon OX-LDL stimulation tested 
      by RT-PCR and Western blot, which was further verified by co-immunofluorescence 
      staining. Next, the loss-of-function of ALK5 used AdshALK5 transfection was 
      performed to test the effect of ALK5 on macrophage activation. We observed that 
      ALK5 silencing inhibited pro-inflammatory but promoted anti-inflammatory 
      macrophage markers expression. Moreover, decreased foam cell formation was found 
      in ALK5 knockdown macrophages accompanied by increased cholesterol efflux. 
      Mechanistically, ALK5 knockdown significantly increased KLF4 expression that was 
      responsible for the attenuated macrophage activation induced by ALK5 knockdown. 
      Collectively, these findings suggested that neutralization of ALK5 may act as a 
      promising strategy for the management of atherosclerosis.
CI  - (c) 2020 The Author(s).
FAU - Li, Wenyan
AU  - Li W
AD  - The First Hospital of Nanchang, Nanchang, 330008, China.
FAU - Wang, Junhua
AU  - Wang J
AD  - The First Hospital of Nanchang, Nanchang, 330008, China.
FAU - Li, Zhaofeng
AU  - Li Z
AD  - The First Hospital of Nanchang, Nanchang, 330008, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
RN  - EC 2.7.11.30 (Tgfbr1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/metabolism
MH  - Cells, Cultured
MH  - Foam Cells/metabolism
MH  - Inflammation/metabolism
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/*metabolism/physiology
MH  - Lipoproteins, LDL/metabolism
MH  - Macrophage Activation
MH  - Macrophages/*immunology/metabolism
MH  - Mice
MH  - Mice, Knockout, ApoE
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Receptor, Transforming Growth Factor-beta Type I/*deficiency/metabolism
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/metabolism
PMC - PMC7056445
OTO - NOTNLM
OT  - ALK5
OT  - KLF4
OT  - foam cell
OT  - inflammation
OT  - macrophage
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2020/02/18 06:00
MHDA- 2021/03/26 06:00
PMCR- 2020/03/04
CRDT- 2020/02/18 06:00
PHST- 2019/12/21 00:00 [received]
PHST- 2020/02/13 00:00 [revised]
PHST- 2020/02/14 00:00 [accepted]
PHST- 2020/02/18 06:00 [pubmed]
PHST- 2021/03/26 06:00 [medline]
PHST- 2020/02/18 06:00 [entrez]
PHST- 2020/03/04 00:00 [pmc-release]
AID - 222146 [pii]
AID - BSR20194188 [pii]
AID - 10.1042/BSR20194188 [doi]
PST - ppublish
SO  - Biosci Rep. 2020 Mar 27;40(3):BSR20194188. doi: 10.1042/BSR20194188.