PMID- 37824022
OWN - NLM
STAT- MEDLINE
DCOM- 20231117
LR  - 20231117
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 80
IP  - 11
DP  - 2023 Oct 12
TI  - Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation 
      after acute myocardial infarction through JAK1-STAT1 signaling.
PG  - 324
LID - 10.1007/s00018-023-04974-7 [doi]
AB  - Immune response plays a crucial role in post-myocardial infarction (MI) 
      myocardial remodeling. Neogenin (Neo1), a multifunctional transmembrane receptor, 
      plays a critical role in the immune response; however, whether Neo1 participates 
      in pathological myocardial remodeling after MI is unclear. Our study found that 
      Neo1 expression changed significantly after MI in vivo and after LPS + IFN-gamma 
      stimulation in bone marrow-derived macrophages (BMDMs) in vitro. Neo1 functional 
      deficiency (using a neutralizing antibody) and macrophage-specific Neo1 
      deficiency (induced by Neo1(flox/flox);Cx3cr1(cre) mice) increased infarction 
      size, enhanced cardiac fibrosis and cardiomyocyte apoptosis, and exacerbated left 
      ventricular dysfunction post-MI in mice. Mechanistically, Neo1 deficiency 
      promoted macrophage infiltration into the ischemic myocardium and transformation 
      to a proinflammatory phenotype, subsequently exacerbating the inflammatory 
      response and impairing inflammation resolution post-MI. Neo1 deficiency regulated 
      macrophage phenotype and function, possibly through the JAK1-STAT1 pathway, as 
      confirmed in BMDMs in vitro. Blocking the JAK1-STAT1 pathway with fludarabine 
      phosphate abolished the impact of Neo1 on macrophage phenotype and function, 
      inflammatory response, inflammation resolution, cardiomyocyte apoptosis, cardiac 
      fibrosis, infarction size and cardiac function. In conclusion, Neo1 deficiency 
      aggravates inflammation and left ventricular remodeling post-MI by modulating 
      macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway. These 
      findings highlight the anti-inflammatory potential of Neo1, offering new 
      perspectives for therapeutic targets in MI treatment. Neo1 deficiency aggravated 
      inflammation and left ventricular remodeling after MI by modulating macrophage 
      phenotypes and functions via the JAK1-STAT1 signaling pathway.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Zhang, Jishou
AU  - Zhang J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Department of 
      Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, 238 Jiefang 
      Road, Wuhan, 430060, China.
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Xu, Yao
AU  - Xu Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Wei, Cheng
AU  - Wei C
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Yin, Zheng
AU  - Yin Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Pan, Wei
AU  - Pan W
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Zhao, Mengmeng
AU  - Zhao M
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Ding, Wen
AU  - Ding W
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
AD  - Department of Radiology, the First Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou, China.
FAU - Xu, Shuwan
AU  - Xu S
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Liu, Jianfang
AU  - Liu J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Yu, Junping
AU  - Yu J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Ye, Jing
AU  - Ye J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Ye, Di
AU  - Ye D
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China.
FAU - Qin, Juan-Juan
AU  - Qin JJ
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Department of 
      Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, 238 Jiefang 
      Road, Wuhan, 430060, China. qinjuanjuan@whu.edu.cn.
AD  - Center for Healthy Aging, Wuhan University School of Nursing, Wuhan, China. 
      qinjuanjuan@whu.edu.cn.
FAU - Wan, Jun
AU  - Wan J
AUID- ORCID: 0000-0003-4865-783X
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Department of 
      Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, 238 Jiefang 
      Road, Wuhan, 430060, China. wanjun@whu.edu.cn.
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China. wanjun@whu.edu.cn.
FAU - Wang, Menglong
AU  - Wang M
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Department of 
      Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, 238 Jiefang 
      Road, Wuhan, 430060, China. whuwangmenglong@163.com.
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key 
      Laboratory of Cardiology, Cardiovascular Research Institute, Wuhan University, 
      Wuhan, China. whuwangmenglong@163.com.
LA  - eng
GR  - 82100292/National Natural Science Foundation of China/
GR  - 82070436/National Natural Science Foundation of China/
GR  - ZNYB2022001/Excellent Doctoral Program of Zhongnan Hospital of Wuhan University/
PT  - Journal Article
DEP - 20231012
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (neogenin)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - 0 (STAT1 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Inflammation/pathology
MH  - Macrophages/metabolism
MH  - Mice, Inbred C57BL
MH  - *Myocardial Infarction/pathology
MH  - Myocardium/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - *Ventricular Remodeling
MH  - Janus Kinase 1/metabolism
MH  - STAT1 Transcription Factor/metabolism
OTO - NOTNLM
OT  - Inflammation resolution
OT  - Myocardial infarction
OT  - Neogenin
OT  - Proinflammatory macrophage
EDAT- 2023/10/12 12:43
MHDA- 2023/11/01 12:42
CRDT- 2023/10/12 11:11
PHST- 2023/02/20 00:00 [received]
PHST- 2023/09/20 00:00 [accepted]
PHST- 2023/09/01 00:00 [revised]
PHST- 2023/11/01 12:42 [medline]
PHST- 2023/10/12 12:43 [pubmed]
PHST- 2023/10/12 11:11 [entrez]
AID - 10.1007/s00018-023-04974-7 [pii]
AID - 10.1007/s00018-023-04974-7 [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2023 Oct 12;80(11):324. doi: 10.1007/s00018-023-04974-7.