PMID- 37431082
OWN - NLM
STAT- MEDLINE
DCOM- 20230915
LR  - 20230916
IS  - 1365-2613 (Electronic)
IS  - 0959-9673 (Print)
IS  - 0959-9673 (Linking)
VI  - 104
IP  - 5
DP  - 2023 Oct
TI  - Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via 
      inhibiting STAT3 expression.
PG  - 237-246
LID - 10.1111/iep.12489 [doi]
AB  - Recently macrophage polarization has emerged as playing an essential role in the 
      oathogenesis of atherosclerosis, which is the most important underlying process 
      in many types of cardiovascular diseases. Although Nek6 has been reported to be 
      involved in various cellular processes, the effect of Nek6 on macrophage 
      polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or 
      IL-4 were used to establish an in vitro model for the study of regulation of 
      classically (M1) or alternatively (M2) activated macrophage. Bone marrow-derived 
      macrophages (BMDMs) transfected with short hairpin RNA-targeting Nek6 were then 
      in functional studies. We observed that Nek6 expression was decreased in both 
      peritoneal macrophages (PMs) and BMDMs stimulated by LPS. This effect was seen at 
      both mRNA and protein level. The opposite results were obtained after 
      administration of IL-4. Macrophage-specific Nek6 knockdown significantly 
      exacerbated pro-inflammatory M1 polarized macrophage gene expression in response 
      to LPS challenge, but the anti-inflammatory response gene expression that is 
      related to M2 macrophages was attenuated by Nek6 silencing followed by treatment 
      with IL-4. Mechanistic studies exhibited that Nek6 knockdown inhibited the 
      phosphorylated STAT3 expression that mediated the effect on macrophage 
      polarization regulated by AdshNek6. Moreover, decreased Nek6 expression was also 
      observed in atherosclerotic plaques. Collectively, these evidences suggested that 
      Nek6 acts as a crucial site in macrophage polarization, and that this operates in 
      a STAT3-dependent manner.
CI  - (c) 2023 Company of the International Journal of Experimental Pathology (CIJEP).
FAU - Wu, Xiaoyan
AU  - Wu X
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Deng, Ke-Qiong
AU  - Deng KQ
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Cai, Huan-Huan
AU  - Cai HH
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Zeng, Ziyue
AU  - Zeng Z
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Cao, Jian-Lei
AU  - Cao JL
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Lu, Zhibing
AU  - Lu Z
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
FAU - Cheng, Wen-Lin
AU  - Cheng WL
AUID- ORCID: 0009-0008-1591-4581
AD  - Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
AD  - Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230710
PL  - England
TA  - Int J Exp Pathol
JT  - International journal of experimental pathology
JID - 9014042
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.1 (NIMA-related kinase 6)
RN  - EC 2.7.11.1 (NIMA-Related Kinases)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Interleukin-4/pharmacology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - *Macrophages/metabolism
MH  - Phenotype
MH  - RNA, Small Interfering
MH  - Animals
MH  - Mice
MH  - *NIMA-Related Kinases/genetics/metabolism
MH  - *STAT3 Transcription Factor/metabolism
PMC - PMC10500168
OTO - NOTNLM
OT  - Nek6
OT  - STAT3
OT  - macrophage polarization
COIS- None.
EDAT- 2023/07/11 06:42
MHDA- 2023/09/15 06:43
PMCR- 2024/07/10
CRDT- 2023/07/11 01:13
PHST- 2023/05/08 00:00 [revised]
PHST- 2023/01/05 00:00 [received]
PHST- 2023/06/18 00:00 [accepted]
PHST- 2024/07/10 00:00 [pmc-release]
PHST- 2023/09/15 06:43 [medline]
PHST- 2023/07/11 06:42 [pubmed]
PHST- 2023/07/11 01:13 [entrez]
AID - IEP12489 [pii]
AID - 10.1111/iep.12489 [doi]
PST - ppublish
SO  - Int J Exp Pathol. 2023 Oct;104(5):237-246. doi: 10.1111/iep.12489. Epub 2023 Jul 
      10.