In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-β1-induced collagen gel contraction

Bolívar, Samir; Espitia-Corredor, Jenaro; Olivares-Silva, Francisco; Valenzuela, Pablo; Humeres, Claudio; Anfossi, Renatto; Castro, Eduardo; Vivar, Raúl; Salas-Hernández, Aimeé; Pardo-Jiménez, V.; Díaz‐Araya, Guillermo

doi:10.1016/j.cyto.2020.155359

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…Neutrophils secrete a variety of cytokines and growth factors, including TGF-β1, which binds to TGF-β1 receptor to activate the TGF-β/Smad pathway in cardiac fibroblast and upregulate transcription of ECM proteins and α-SMA. These ECM proteins are converted into myofibroblasts, 21 and the extracellular deposition of a large number of these ECM proteins will form fibrotic scar tissue, which is tough and inflexible, thus leading to pathological changes in the heart, such as myocardial infarction, heart failure, arrhythmia and other cardiovascular diseases. 22 TGF-β/Smad pathway is the most classic pathway to induce myocardial fibrosis, TGF-β1 and IITGF-β receptor (TβRII) binding, therefore TβRII is activated.…”

Section: Discussionmentioning

confidence: 99%

Preparation, characterization and in vitro study of bellidifolin nano-micelles

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Preparation, characterization and in vitro study of bellidifolin nano-micelles

et al. 2022

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“…Senescent T cells are more pro-inflammatory and, when injected into young lymphocyte-deficient mice, show higher cardiac tropism than young T cells; however, they are not sufficient to cause major functional and structural cardiac alterations [ 29 , 34 ]. Immune cells are the major source of both IFN-γ and IFN-β; however, the latter can also be produced by non-immune cells, including cardiac cells [ 35 , 36 ]. IFN-β has a well-established protective role in the heart; indeed, myocardial lesions induced by different types of viruses can be reduced by IFN-β treatment [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, IFN-γ can inhibit proliferation and the expression of profibrotic genes in human cardiac myofibroblasts [ 40 ]. Similarly, IFN-β can counteract the profibrotic activity of TGF-β1 through STAT1 and STAT2 activation in cardiac fibroblasts [ 35 ]. Herein, we show that physiological cardiac aging in WT animals is associated with the down-regulation of T-cell activation and IFN signaling pathways, and their earlier impairment, observed in Young Rage−/− animals, causes an acceleration of age-dependent cardiac remodeling, in particular fibrosis, suggesting a protective function of T cell-mediated type I response during heart aging.…”

Section: Discussionmentioning

confidence: 99%

Effects of RAGE Deletion on the Cardiac Transcriptome during Aging

Scavello

Piacentini

Castiglione

et al. 2022

IJMS

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Cardiac aging is characterized by increased cardiomyocyte hypertrophy, myocardial stiffness, and fibrosis, which enhance cardiovascular risk. The receptor for advanced glycation end-products (RAGE) is involved in several age-related diseases. RAGE knockout (Rage−/−) mice show an acceleration of cardiac dimension changes and interstitial fibrosis with aging. This study identifies the age-associated cardiac gene expression signature induced by RAGE deletion. We analyzed the left ventricle transcriptome of 2.5-(Young), 12-(Middle age, MA), and 21-(Old) months-old female Rage−/− and C57BL/6N (WT) mice. By comparing Young, MA, and Old Rage−/− versus age-matched WT mice, we identified 122, 192, and 12 differently expressed genes, respectively. Functional inference analysis showed that RAGE deletion is associated with: (i) down-regulation of genes involved in antigen processing and presentation of exogenous antigen, adaptive immune response, and cellular responses to interferon beta and gamma in Young animals; (ii) up-regulation of genes related to fatty acid oxidation, cardiac structure remodeling and cellular response to hypoxia in MA mice; (iii) up-regulation of few genes belonging to complement activation and triglyceride biosynthetic process in Old animals. Our findings show that the age-dependent cardiac phenotype of Rage−/− mice is associated with alterations of genes related to adaptive immunity and cardiac stress pathways.

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“…TGF-β1 is a critical regulator of tissue growth, regeneration, remodeling, and fibrosis. TGF-β1 in the injured heart is expressed by resident macrophages and cardiac fibroblasts [ 34 ]. Through the activation of the downstream Smad pathway, TGF-β1 induces cardiac fibroblast to myofibroblast differentiation and collagen deposition [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats

Day

et al. 2021

Open Life Sciences

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The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world’s population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been classified as carcinogenic to humans as it adversely affects various organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. Earlier studies have established a link between areca nut chewing and cardiac arrhythmias, and yet research pertaining to the mechanisms underlying cardiotoxicity caused by arecoline is still preliminary. The main purpose of this study is to test the hypothesis that arecoline causes cardiac fibrosis through transforming growth factor-β (TGF-β)/Smad-mediated signaling pathways. Male Wistar rats were injected intraperitoneally with low (5 mg/kg/day) or high (50 mg/kg/day) doses of arecoline for 3 weeks. Results from Masson’s trichrome staining indicated that arecoline could induce cardiac fibrosis through collagen accumulation. Western blot analysis showed that TGF-β and p-Smad2/3 protein expression levels were markedly higher in the arecoline-injected rat hearts than in those of the control rats. Moreover, arecoline upregulated other fibrotic-related proteins, including SP1-mediated connective tissue growth factor expression. Tissue-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, and matrix metalloproteinase (MMP) 9 were upregulated, and the inhibitor of MMP9 was downregulated. This study provides novel insight into the molecular mechanisms underlying arecoline-induced cardiac fibrosis. Taken together, the areca nut is a harmful substance, and the detrimental effects of arecoline on the heart are similar to that caused by oral submucous fibrosis.

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In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-β1-induced collagen gel contraction

Cited by 11 publications

References 37 publications

Preparation, characterization and in vitro study of bellidifolin nano-micelles

Preparation, characterization and in vitro study of bellidifolin nano-micelles

Effects of RAGE Deletion on the Cardiac Transcriptome during Aging

The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats

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