The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

Matsumoto, K.; Aoki, Hiroki

doi:10.3389/fimmu.2020.609752

Cited by 29 publications

(19 citation statements)

References 136 publications

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“…In our study we did not find a difference in morphological pathology caused by infection. It has recently been reviewed that the role of TNC is highly context-dependent, and while it is often associated with an enhanced immune response and increased tissue damage, TNC can also play an immune-suppressive role depending on both the inflammatory context and the splicoform expressed ( 37 ). Thus, subtle changes in pulmonary morphology and signaling could alter the microenvironment and affect bacterial proliferation and dissemination, as well as the form and function of the TNC protein.…”

Section: Discussionmentioning

confidence: 99%

Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice

et al. 2021

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Tenascin C (TNC) is an extracellular matrix glycoprotein that recently emerged as an immunomodulator. TNC-deficient (TNC−/−) mice were reported to have a reduced inflammatory response upon systemic administration of lipopolysaccharide, the toxic component of gram-negative bacteria. Here, we investigated the role of TNC during gram-negative pneumonia derived sepsis. TNC+/+ and TNC−/− mice were infected with Klebsiella pneumoniae via the airways and sacrificed 24 and 42 h thereafter for further analysis. Pulmonary TNC protein levels were elevated 42 h after infection in TNC+/+ mice and remained undetectable in TNC−/− mice. TNC−/− mice showed modestly lower bacterial loads in lungs and blood, and a somewhat reduced local—but not systemic—inflammatory response. Moreover, TNC−/− and TNC+/+ mice did not differ with regard to neutrophil recruitment, lung pathology or plasma markers of distal organ injury. These results suggest that while TNC shapes the immune response during lipopolysaccharide-induced inflammation, this role may be superseded during pneumosepsis caused by a common gram-negative pathogen.

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Section: Discussionmentioning

confidence: 99%

Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice

et al. 2021

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“…The deletion of TNC may attenuate the severity of myocarditis by reducing Th17 cell infiltration in the mouse heart [ 55 ], suggesting that TNC adversely affects the status of myocarditis; however, it may also have an immunosuppressive function depending on both the inflammatory context and splicoform expressed [ 15 , 149 ].…”

Section: Myocarditismentioning

confidence: 99%

“…An increasing number of studies have examined the clinical utility of serum TNC levels in patients with various heart diseases (reviewed in [ 149 , 174 , 175 ]), such as non-compaction/hypertrabeculation [ 176 ], hypertrophic cardiomyopathy [ 177 ], heart failure with ischemic heart disease, Kawasaki disease [ 178 ], rheumatic heart disease, and congenital heart disease in pediatric patients [ 179 , 180 ].…”

Section: Clinical Application Of Tncmentioning

confidence: 99%

Tenascin-C in Heart Diseases—The Role of Inflammation

Imanaka‐Yoshida

2021

IJMS

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Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

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“…In addition of increased IL-6 expression and p38 MAPK phosphorylation, we show an increased TNC expression in cardiac fibroblasts of PIEZO1 M-R/M-R mice treated with Yoda1. TNC is mostly absent in normal adult heart but re-expressed under pathological conditions, such as dilated cardiomyopathy, myocarditis or myocardial infarction [ 79 , 80 , 81 , 82 ]. The major source of TNC in the heart is fibroblasts and this protein is implicated in myofibroblast differentiation [ 80 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice

Bartoli

Evans

Blythe

et al. 2022

Cells

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PIEZO1 is a subunit of mechanically-activated, nonselective cation channels. Gain-of-function PIEZO1 mutations are associated with dehydrated hereditary stomatocytosis (DHS), a type of anaemia, due to abnormal red blood cell function. Here, we hypothesised additional effects on the heart. Consistent with this hypothesis, mice engineered to contain the M2241R mutation in PIEZO1 to mimic a DHS mutation had increased cardiac mass and interventricular septum thickness at 8–12 weeks of age, without altered cardiac contractility. Myocyte size was greater and there was increased expression of genes associated with cardiac hypertrophy (Anp, Acta1 and β-MHC). There was also cardiac fibrosis, increased expression of Col3a1 (a gene associated with fibrosis) and increased responses of isolated cardiac fibroblasts to PIEZO1 agonism. The data suggest detrimental effects of excess PIEZO1 activity on the heart, mediated in part by amplified PIEZO1 function in cardiac fibroblasts.

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The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

Cited by 29 publications

References 136 publications

Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice

Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth During Klebsiella pneumoniae-Evoked Pneumosepsis in Mice

Tenascin-C in Heart Diseases—The Role of Inflammation

Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice

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