PMID- 34957094
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211228
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through 
      Inhibition of Myocardial Fibrosis in Diabetic Mice.
PG  - 757068
LID - 10.3389/fcell.2021.757068 [doi]
LID - 757068
AB  - The incidence of type 2 diabetes mellitus (T2DM) has been increasing globally, 
      and T2DM patients are at an increased risk of major cardiac events such as 
      myocardial infarction (MI). Nevertheless, the molecular mechanisms underlying MI 
      injury in T2DM remain elusive. Ubiquitin-specific protease 10 (USP10) functions 
      as a NICD1 (Notch1 receptor) deubiquitinase that fine-tunes the essential 
      myocardial fibrosis regulator Notch signaling. Follistatin-like protein 1 (FSTL1) 
      is a cardiokine with proven benefits in multiple pathological processes including 
      cardiac fibrosis and insulin resistance. This study was designed to examine the 
      roles of FSTL1/USP10/Notch1 signaling in MI-induced cardiac dysfunction in T2DM. 
      High-fat-diet-treated, 8-week-old C57BL/6J mice and db/db T2DM mice were used. 
      Intracardiac delivery of AAV9-FSTL1 was performed in T2DM mice following MI 
      surgery with or without intraperitoneal injection of crenigacestat (LY3039478) 
      and spautin-1. Our results demonstrated that FSTL1 improved cardiac function 
      following MI under T2DM by reducing serum lactate dehydrogenase (LDH) and 
      myocardial apoptosis as well as cardiac fibrosis. Further in vivo studies 
      revealed that the protective role of FSTL1 against MI injury in T2DM was mediated 
      by the activation of USP10/Notch1. FSTL1 protected cardiac fibroblasts (CFs) 
      against DM-MI-induced cardiofibroblasts injury by suppressing the levels of 
      fibrosis markers, and reducing LDH and MDA concentrations in a 
      USP10/Notch1-dependent manner. In conclusion, FSTL1 treatment ameliorated cardiac 
      dysfunction in MI with co-existent T2DM, possibly through inhibition of 
      myocardial fibrosis and apoptosis by upregulating USP10/Notch1 signaling. This 
      finding suggests the clinical relevance and therapeutic potential of FSTL1 in 
      T2DM-associated MI and other cardiovascular diseases.
CI  - Copyright (c) 2021 Lu, Ma, Liu, Shao, Xiong, Duan, Gao, Yang, Chen, Yang, Ren, 
      Zheng and Liu.
FAU - Lu, Linhe
AU  - Lu L
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Ma, Jipeng
AU  - Ma J
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Shao, Yalan
AU  - Shao Y
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Xiong, Xiang
AU  - Xiong X
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Duan, Weixun
AU  - Duan W
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Gao, Erhe
AU  - Gao E
AD  - Center for Translational Medicine, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA, United States.
FAU - Yang, Qianli
AU  - Yang Q
AD  - Department of Ultrasound, Xijing Hospital, The Air Force Medical University, 
      Xi'an, China.
FAU - Chen, Shasha
AU  - Chen S
AD  - Department of Ultrasound, Xijing Hospital, The Air Force Medical University, 
      Xi'an, China.
FAU - Yang, Jian
AU  - Yang J
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
FAU - Ren, Jun
AU  - Ren J
AD  - Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital Fudan University, Shanghai, China.
AD  - Department of Clinical Medicine and Pathology, University of Washington, Seattle, 
      WA, United States.
FAU - Zheng, Qijun
AU  - Zheng Q
AD  - Department of Cardiovascular Surgery, Shenzhen People's Hospital, The Second 
      Clinical Medical College, Jinan University, Shenzhen, China.
FAU - Liu, Jincheng
AU  - Liu J
AD  - Department of Cardiovascular Surgery, Xijing Hospital, The Air Force Medical 
      University, Xi'an, China.
LA  - eng
PT  - Journal Article
DEP - 20211209
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8695978
OTO - NOTNLM
OT  - apoptosis
OT  - diabetes cardiomyopathy
OT  - fibrosis
OT  - follistatin-like protein 1
OT  - myocardial infarction
OT  - ubiquitin-specific protease 10
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/28 06:00
MHDA- 2021/12/28 06:01
PMCR- 2021/01/01
CRDT- 2021/12/27 06:33
PHST- 2021/08/18 00:00 [received]
PHST- 2021/11/17 00:00 [accepted]
PHST- 2021/12/27 06:33 [entrez]
PHST- 2021/12/28 06:00 [pubmed]
PHST- 2021/12/28 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 757068 [pii]
AID - 10.3389/fcell.2021.757068 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Dec 9;9:757068. doi: 10.3389/fcell.2021.757068. 
      eCollection 2021.