PMID- 37120549
OWN - NLM
STAT- MEDLINE
DCOM- 20230510
LR  - 20230522
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Apr 29
TI  - OSMR deficiency aggravates pressure overload-induced cardiac hypertrophy by 
      modulating macrophages and OSM/LIFR/STAT3 signalling.
PG  - 290
LID - 10.1186/s12967-023-04163-x [doi]
LID - 290
AB  - BACKGROUND: Oncostatin M (OSM) is a secreted cytokine of the interleukin (IL)-6 
      family that induces biological effects by activating functional receptor 
      complexes of the common signal transducing component glycoprotein 130 (gp130) and 
      OSM receptor beta (OSMR) or leukaemia inhibitory factor receptor (LIFR), which are 
      mainly involved in chronic inflammatory and cardiovascular diseases. The effect 
      and underlying mechanism of OSM/OSMR/LIFR on the development of cardiac 
      hypertrophy remains unclear. METHODS AND RESULTS: OSMR-knockout (OSMR-KO) mice 
      were subjected to aortic banding (AB) surgery to establish a model of pressure 
      overload-induced cardiac hypertrophy. Echocardiographic, histological, 
      biochemical and immunological analyses of the myocardium and the adoptive 
      transfer of bone marrow-derived macrophages (BMDMs) were conducted for in vivo 
      studies. BMDMs were isolated and stimulated with lipopolysaccharide (LPS) for the 
      in vitro study. OSMR deficiency aggravated cardiac hypertrophy, fibrotic 
      remodelling and cardiac dysfunction after AB surgery in mice. Mechanistically, 
      the loss of OSMR activated OSM/LIFR/STAT3 signalling and promoted a proresolving 
      macrophage phenotype that exacerbated inflammation and impaired cardiac repair 
      during remodelling. In addition, adoptive transfer of OSMR-KO BMDMs to WT mice 
      after AB surgery resulted in a consistent hypertrophic phenotype. Moreover, 
      knockdown of LIFR in myocardial tissue with Ad-shLIFR ameliorated the effects of 
      OSMR deletion on the phenotype and STAT3 activation. CONCLUSIONS: OSMR deficiency 
      aggravated pressure overload-induced cardiac hypertrophy by modulating 
      macrophages and OSM/LIFR/STAT3 signalling, which provided evidence that OSMR 
      might be an attractive target for treating pathological cardiac hypertrophy and 
      heart failure.
CI  - (c) 2023. The Author(s).
FAU - Feng, Yizhou
AU  - Feng Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Yuan, Yuan
AU  - Yuan Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Xia, Hongxia
AU  - Xia H
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Wang, Zhaopeng
AU  - Wang Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Che, Yan
AU  - Che Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Hu, Zhefu
AU  - Hu Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Deng, Jiangyang
AU  - Deng J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Li, Fangfang
AU  - Li F
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Wu, Qingqing
AU  - Wu Q
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Bian, Zhouyan
AU  - Bian Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Zhou, Heng
AU  - Zhou H
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Shen, Difei
AU  - Shen D
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
FAU - Tang, Qizhu
AU  - Tang Q
AUID- ORCID: 0000-0003-2210-3169
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, 
      China. qztang@whu.edu.cn.
AD  - Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, China. 
      qztang@whu.edu.cn.
AD  - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. 
      qztang@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230429
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Interleukin-6)
RN  - 106956-32-5 (Oncostatin M)
RN  - 0 (Receptors, OSM-LIF)
RN  - 0 (Receptors, Oncostatin M)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Cardiomegaly
MH  - *Interleukin-6
MH  - Macrophages
MH  - Oncostatin M/genetics
MH  - *Receptors, OSM-LIF/genetics
MH  - *Signal Transduction
MH  - *Receptors, Oncostatin M/genetics
PMC - PMC10149029
OTO - NOTNLM
OT  - Heart failure
OT  - Hypertrophy
OT  - LIFR
OT  - Macrophage
OT  - OSMR
COIS- The authors declare that they have no competing interests.
EDAT- 2023/04/30 00:42
MHDA- 2023/05/01 11:42
PMCR- 2023/04/29
CRDT- 2023/04/29 23:15
PHST- 2022/12/10 00:00 [received]
PHST- 2023/04/26 00:00 [accepted]
PHST- 2023/05/01 11:42 [medline]
PHST- 2023/04/30 00:42 [pubmed]
PHST- 2023/04/29 23:15 [entrez]
PHST- 2023/04/29 00:00 [pmc-release]
AID - 10.1186/s12967-023-04163-x [pii]
AID - 4163 [pii]
AID - 10.1186/s12967-023-04163-x [doi]
PST - epublish
SO  - J Transl Med. 2023 Apr 29;21(1):290. doi: 10.1186/s12967-023-04163-x.