Follistatin‐like 1: A dual regulator that promotes cardiomyocyte proliferation and fibrosis

Hu, Siyuan; Liu, Hua; Hu, Zhixi; Lin, Liang‐Chuan; Yang, Yi

doi:10.1002/jcp.29588

Cited by 17 publications

(10 citation statements)

References 79 publications

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“…It was further confirmed that FSTL1 delivered through an epicardial patch protected the heart against MI injury by promoting cardiomyocyte division ( Wei et al, 2015 ). Further, FSTL1 protected the heart against MI injury by decreasing myocardial fibrosis, and protected the heart from rupture by regulating cardiac fibroblast activation ( Rainer et al, 2014 ; Maruyama et al, 2016 ; Xiao et al, 2019 ; Hu et al, 2020 ). Importantly, upregulation of FSTL1 secretion induced by exercise training alleviated cardiac dysfunction resulting from MI injury by TGFβ-Smad2/3 induced angiogenesis ( Xi et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…If there has a therapeutic strategy that can balance this pathological change? Previous studies have suggested that FSTL1 attenuated pathological injury of multiple organs by alleviating fibrosis, particularly in cardiac dysfunction ( Jiang et al, 2020 ; Hu et al, 2020 ; Li et al, 2021 ; Z.; Chen Z. et al, 2019 ; Yang et al, 2020 ). Our current findings are consistent with these aforementioned research findings that the upregulation of FSTL1 in DM compared with the control group, which was further increased in T2DM with MI.…”

Section: Discussionmentioning

confidence: 99%

“…FSTL1 insufficiency leads to venous wall and atrial fibrosis by switching on SMAD3 signaling ( Jiang et al, 2020 ). Further, Wei et al applied an epicardial patch with human FSTL1 protein to rescue cardiac dysfunction in swine and mouse MI models through inhibition of myocardial fibrosis ( Wei et al, 2015 ; Shen et al, 2019 ; Hu et al, 2020 ; Xi et al, 2020 ). FSTL1 was also implicated in the regulation of insulin resistance and circulating FSTL1 levels were elevated in patients with T2DM ( Xu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice

Yang

et al. 2021

Front. Cell Dev. Biol.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice

Yang

et al. 2021

Front. Cell Dev. Biol.

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“…For the factors related to the myocardial repair, several growth factors [35,36] have been found to promote the proliferation of cardiomyocytes, but they have the risk to cause cardiac fibrosis. microRNAs [7,11] also show effects in stimulated cardiomyocytes proliferation in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Wang

et al. 2020

Preprint

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Mammal cardiomyocytes lose their ability of regeneration shortly after birth. Reduced cardiomyocytes number caused by myocardial damage is unable to reverse in current clinical therapies. Therefore, it is important and urgent to find new approaches to stimulate cardiomyocytes regeneration. Here we design a recombinant protein IGF1-24 and show that it triggers cardiomyocytes proliferation in rat. 7 days after tail intravenous injection of IGF1-24 ， 6-7-weeks-old healthy rats showed marked improvements in cardiomyocytes proliferation. Next, we injured rats cardiac with isoproterenol and treated them with IGF1-24 injection. We found that it efficiently induced cell proliferation with significant improvements in heart histology. These results show that the recombinant IGF1-24 stimulates cardiomyocytes proliferation and can be used to achieve cardiac repair through stimulating endogenous cardiomyocyte proliferation in rats. The IGF 1-24 could be a prospective medicine to heart repair because it has high efficiency in triggering cell proliferation and it can be easily applied to heart by intravenous injection

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“…It manifests as deposition of scar, increasing stiffness, decreasing contraction and impaired heart function, which ultimately resulting in heart failure (116). Although, cardiac fibrosis is a complex process and involves many types of cells in the heart, such as cardiomyocytes, fibroblasts, lymphocytes, and pericytes (117)(118)(119), extensive studies have proved that cardiac fibroblasts (CFs) play a pivotal role in this process (120). When suffered cardiac injury, the proliferation and migration of CFs are increased.…”

Section: Circular Rnas In the Activation Of Cardiac Fibroblastsmentioning

confidence: 99%

Circle the Cardiac Remodeling With circRNAs

Yang

Long

et al. 2021

Front. Cardiovasc. Med.

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Cardiac remodeling occurs after the heart is exposed to stress, which is manifested by pathological processes such as cardiomyocyte hypertrophy and apoptosis, dendritic cells activation and cytokine secretion, proliferation and activation of fibroblasts, and finally leads to heart failure. Circular RNAs (circRNAs) are recently recognized as a specific type of non-coding RNAs that are expressed in different species, in different stages of development, and in different pathological conditions. Growing evidences have implicated that circRNAs play important regulatory roles in the pathogenesis of a variety of cardiovascular diseases. In this review, we summarize the biological origin, characteristics, functional classification of circRNAs and their regulatory functions in cardiomyocytes, endothelial cells, fibroblasts, immune cells, and exosomes in the pathogenesis of cardiac remodeling.

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Follistatin‐like 1: A dual regulator that promotes cardiomyocyte proliferation and fibrosis

Abstract: Follistatin-like 1 (FSTL1) is a key factor in maintaining cardiac growth and development.

Cited by 17 publications

References 79 publications

FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice

FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice

Recombinant Protein IGF1-24 Stimulates Rat Cardiomyocytes Proliferation and Repairs Myocardial Injury

Circle the Cardiac Remodeling With circRNAs

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