Long noncoding RNA TUG1 promotes cardiac fibroblast transformation to myofibroblasts via miR‑29c in chronic hypoxia

Zhu, Yun; Feng, Zezhou; Zhao, Jian; Ye, Xiao

doi:10.3892/mmr.2018.9327

Cited by 24 publications

(26 citation statements)

References 37 publications

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“…Therefore, a limitation of the present study is that only ten heart samples were collected for each group. It has been accepted that mammalian cells have developed an adaptive mechanism to activate prosurvival signalling pathways to cope with oxygen level decrease or oxygen deficiency (25,26). Therefore, it can be speculated that upregulation of Sirt1 could be a compensatory mechanism by which cardiomyocytes cope with hypoxic stress.…”

Section: Discussionmentioning

confidence: 99%

Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress

et al. 2019

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Sirtuin 1 (Sirt1) exerts its cardioprotective effects in various cardiovascular diseases via multiple cellular activities. However, the therapeutic implications of Sirt1 in hypoxic cardiomyocytes and the underlying mechanisms remain elusive. The present study investigated whether Sirt1 regulates autophagy and apoptosis in hypoxic H9C2 cardiomyocytes and in an experimental hypoxic mouse model. Right ventricular outflow tract biopsies were obtained from patients with cyanotic or acyanotic congenital heart diseases. Adenovirus Ad-Sirt1 was used to activate Sirt1 and Ad-Sh-Sirt1 was used to inhibit Sirt1 expression in H9C2 cells, in order to investigate the effect of Sirt1 on cellular autophagy and apoptosis. SRT1720, a pharmacological activator of Sirt1 and EX-527, a Sirt1 antagonist, were administered to mice to explore the role of Sirt1 in hypoxic cardiomyocytes in viv o. The levels of autophagy and apoptosis-related proteins were evaluated using western blotting. Apoptosis was investigated by TUNEL staining and Annexin V/7-aminoactinomycin D flow cytometry analysis. Heart tissue samples from cyanotic patients exhibited increased autophagy and apoptosis, as well as elevated Sirt1 levels, compared with the noncyanotic control samples. The data from the western blot analysis revealed that Sirt1 promoted autophagic flux and reduced apoptosis in hypoxic H9C2 cells. In addition, Sirt1 activated AMP-activated protein kinase (AMPK), and the AMPK inhibitor Compound C abolished the effect of Sirt1 on autophagy activation. Further exploration of the mechanism revealed that Sirt1 protects hypoxic cardiomyocytes from apoptosis, at least in part, through inositol requiring kinase enzyme 1α (IRE1α). Consistent with the in vitro results, treatment with the Sirt1 activator SRT1720 activated AMPK, inhibited IRE1α, enhanced autophagy, and decreased apoptosis in the heart tissues of normoxic mice compared with the hypoxia control group. Opposite changes were observed in hypoxic mice treated with the Sirt1 inhibitor EX-527. These results suggested that Sirt1 promoted autophagy via AMPK activation and reduced hypoxia-induced apoptosis via the IRE1α pathway, to protect cardiomyocytes from hypoxic stress.

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Section: Discussionmentioning

confidence: 99%

Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress

et al. 2019

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“…High glucose/human CFs Anti [191] miR-154 Up Suppress GSK-3β/ Activate WNT signaling Human CFs Pro [192] miR-154 Up Suppress DKK2/ Activate WNT signaling Human CFs Pro [193] miR-199a Up Suppress secreted frizzled-related protein 5 (SFRP5) ISO, Rat CFs Pro [194] miR-503 Up Activate connective tissue growth factor (CTGF) and TGF-β AngII, TAC/mouse; CFs Pro [195] [197] Homeobox A11 antisense (HOXA11-AS)…”

Section: The Relationship Between Ncrnas and Tgfβ And/ Or Wnt Signalimentioning

confidence: 99%

TGF-β and WNT signaling pathways in cardiac fibrosis: non-coding RNAs come into focus

et al. 2020

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Cardiac fibrosis describes the inappropriate proliferation of cardiac fibroblasts (CFs), leading to accumulation of extracellular matrix (ECM) proteins in the cardiac muscle, which is found in many pathophysiological heart conditions. A range of molecular components and cellular pathways, have been implicated in its pathogenesis. In this review, we focus on the TGF-β and WNT signaling pathways, and their mutual interaction, which have emerged as important factors involved in cardiac pathophysiology. The molecular and cellular processes involved in the initiation and progression of cardiac fibrosis are summarized. We focus on TGF-β and WNT signaling in cardiac fibrosis, ECM production, and myofibroblast transformation. Non-coding RNAs (ncRNAs) are one of the main players in the regulation of multiple pathways and cellular processes. MicroRNAs, long non-coding RNAs, and circular long non-coding RNAs can all interact with the TGF-β/WNT signaling axis to affect cardiac fibrosis. A better understanding of these processes may lead to new approaches for diagnosis and treatment of many cardiac conditions.

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“…Recently, TUG1 is also reported to exert a crucial regulation in the processes of cardiovascular diseases. TUG1 is increased during cardiac fibroblast‐myofibroblast transformation (FMT) and inhibition of TUG1 ameliorates FMT through sponging miR‐29c . TUG1 contributes to cerebral ischaemia/reperfusion injury by sponging miR‐145 to up‐regulate AQP4 expression .…”

Section: Introductionmentioning

confidence: 99%

LncRNA TUG1 alleviates cardiac hypertrophy by targeting miR‐34a/DKK1/Wnt‐β‐catenin signalling

Fang

Liu

et al. 2020

J Cellular Molecular Medi

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Cardiac hypertrophy, classified as physiological and pathological hypertrophy, is an adaptive response of the heart to keep normal cardiac function in the condition of pathological injury or abnormal stress. 1 Physiological cardiac hypertrophy, caused by pregnancy or sports training, has normal morphological characteristics and helpful influences on the heart. 2 Pathological cardiac hypertrophy, accompanied by maladaptive cardiac remodelling, altered cardiac morphology as well as abnormal cardiac gene expressions, is the key induction factor for heart failure progression. 3 Although many factors have been confirmed to induce cardiac hypertrophy, 4 the underlying molecular mechanisms have not been stated clearly. LncRNAs, a series of highly conserved non-coding RNAs, are composed of more than 200 nucleotides. 5,6 With continuous advances in sequencing technology and large-scale genome sequencing projects, Abstract The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β-catenin signalling.In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy. K E Y W O R D Scardiac hypertrophy, DKK 1, lncRNA TUG1, miR-34a, Wnt/β-catenin signalling

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Long noncoding RNA TUG1 promotes cardiac fibroblast transformation to myofibroblasts via miR‑29c in chronic hypoxia

Cited by 24 publications

References 37 publications

Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress

Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress

TGF-β and WNT signaling pathways in cardiac fibrosis: non-coding RNAs come into focus

LncRNA TUG1 alleviates cardiac hypertrophy by targeting miR‐34a/DKK1/Wnt‐β‐catenin signalling

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