TSC-22 up-regulates collagen 3a1 gene expression in the rat heart

Kelloniemi, Annina; Aro, Jani; Näpänkangas, Juha; Koivisto, Elina; Mustonen, Erno; Ruskoaho, Heikki; Rysä, Jaana

doi:10.1186/s12872-015-0121-2

Cited by 2 publications

(2 citation statements)

References 54 publications

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“…Qun Chen et al reported that NEAT1 bind to EZH2 to suppress the Wnt signaling pathway and thereby regulated Glioblastoma progression[ 49 ]. Considering that our in vitro cellular model of cardiac fibrosis was stimulated using TGF-β1, and Smad7 is a very classical key antagonist of the reported TGF-β1/Smad2/3 signaling pathway [ 50 , 51 ], which is normally considered to inhibit Smad2, Smad3, and Smad4 [ 52 ], thereby suppressing the progression of many fibrotic diseases, has also been reported to be inhibited by binding to EZH2 [ 53 ]. Therefore, we chose Smad7 as a downstream molecule for this study.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region

Yin

et al. 2022

J Transl Med

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Cardiac fibrosis, a well-known major pathological process that ultimately leads to heart failure, has attracted increasing attention and focus in recent years. A large amount of research indicates that long noncoding RNAs (lncRNAs) play an important role in cardiac fibrosis, but little is known about the specific function and mechanism of the lncRNA NEAT1 in the progression of cardiac fibrosis to heart failure. In the present study, we have demonstrated that the lncRNA NEAT1 is upregulated in patients with heart failure. Similarly, the expression of Neat1 was also increased in the left ventricular tissue of transverse aortic constriction (TAC) surgery mice and cardiac fibroblasts treated with TGF-β1. Further, gain-of-function and loss-of-function experiments showed that silencing of Neat1 attenuated cardiac fibrosis, while overexpression of Neat1 with adenovirus significantly aggravated the in vitro progression of fibrosis. With regard to the underlying mechanism, our experiments showed that Neat1 recruited EZH2 to the promoter region of Smad7 through physical binding of EZH2 to the promoter region, as a result of which Smad7 expression was inhibited and the progression of cardiac fibrosis was ultimately exacerbated. We found that the introduction of shNeat1 carried by adeno-associated virus-9 significantly ameliorated cardiac fibrosis and dysfunction caused by TAC surgery in mice. Overall, our study findings demonstrate that the lncRNA Neat1 accelerates the progression of cardiac fibrosis and dysfunction by recruiting EZH2 to suppress Smad7 expression. Thus, NEAT1 may serve as a target for the treatment of cardiac fibrosis.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region

Yin

et al. 2022

J Transl Med

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“…Transforming Growth Factor Beta-1-Induced Transcript 4 Protein (Tsc22; upregulated in MCT RV: protein = 3.82-fold, transcript = 2.1-fold) Tsc22 regulates alpha smooth muscle actin, PAI-1, fibronectin and collagen I, contributing to myocardial fibrosis ( Yan et al, 2011 ). Tsc22 is also upregulated in the left ventricle of spontaneously hypertensive rats (SHR), in experimental myocardial infarction models and in models of LVH caused by chronic pressure overload driven by either arginine vasopressin or angiotensin II ( Kelloniemi et al, 2015 ). While adenoviral overexpression of TCS22 failed to significantly regulate many heart failure-relevant transcripts (including brain natriuretic peptide, Anp, Il6 and Col1a), it did elicit a robust increase in Col3a1 in the LV.…”

Section: Discussionmentioning

confidence: 99%

An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats

Hindmarch

Tian²,

Xiong³

et al. 2022

Front. Physiol.

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Aim: Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy that results in death from right ventricular failure (RVF). There is limited understanding of the molecular mechanisms of RVF in PAH.Methods: In a PAH-RVF model induced by injection of adult male rats with monocrotaline (MCT; 60 mg/kg), we performed mass spectrometry to identify proteins that change in the RV as a consequence of PAH induced RVF. Bioinformatic analysis was used to integrate our previously published RNA sequencing data from an independent cohort of PAH rats.Results: We identified 1,277 differentially regulated proteins in the RV of MCT rats compared to controls. Integration of MCT RV transcriptome and proteome data sets identified 410 targets that are concordantly regulated at the mRNA and protein levels. Functional analysis of these data revealed enriched functions, including mitochondrial metabolism, cellular respiration, and purine metabolism. We also prioritized 15 highly enriched protein:transcript pairs and confirmed their biological plausibility as contributors to RVF. We demonstrated an overlap of these differentially expressed pairs with data published by independent investigators using multiple PAH models, including the male SU5416-hypoxia model and several male rat strains.Conclusion: Multiomic integration provides a novel view of the molecular phenotype of RVF in PAH which includes dysregulation of pathways involving purine metabolism, mitochondrial function, inflammation, and fibrosis.

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TSC-22 up-regulates collagen 3a1 gene expression in the rat heart

Cited by 2 publications

References 54 publications

Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region

Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region

An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats

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