LncRNA GAS5 controls cardiac fibroblast activation and fibrosis by targeting miR-21 via PTEN/MMP-2 signaling pathway

Tao, Hui; Zhang, Jia-Gui; Qin, Run-He; Dai, Chen; Shi, Peng; Yang, Jingjing; Deng, Zhiping; Shi, Kai-Hu

doi:10.1016/j.tox.2017.05.007

Cited by 134 publications

(116 citation statements)

References 20 publications

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“…ROS triggers activation of PI3K/AKT/mTOR pathways in peritoneal MCs, a key step in the process of peritoneal fibrosis . As an important tumor suppressor, PTEN also is considered to be an important anti‐fibrotic molecule . Increasing evidence shows that PTEN may play important roles in the fibrosis of multiple organs.…”

Section: Discussionmentioning

confidence: 99%

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

Chen

Liu

et al. 2020

FASEB j.

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As a convenient, effective and economical kidney replacement therapy for end‐stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long‐term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose‐induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen‐rich peritoneal dialysate. In addition, in vitro studies of high glucose‐induced peritoneal fibrosis were performed using MeT‐5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti‐peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.

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Section: Discussionmentioning

confidence: 99%

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

Chen

Liu

et al. 2020

FASEB j.

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“…The differentiation and proliferation for cardiac fibroblasts is the main reason of cardiac fibrosis. Hence, these findings may indicate that the modulation of miR‐21/PTEN by GAS5 plays an important role in the development of cardiac fibrosis …”

Section: Lncrna As Mirna Sponges In Regulating the Biological Activitmentioning

confidence: 99%

The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

Huang

2018

J Cellular Molecular Medi

395

288

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Long noncoding RNAs (lncRNAs) are RNAs longer than 200 nt in length that are characterized by low levels of sequence conservation and expression; lncRNAs modulate various biological functions at epigenetic, transcriptional and post‐transcriptional levels, or directly regulate protein activity. As a family of small and evolutionarily conserved noncoding RNAs, microRNAs (miRNAs) are capable of regulating physiological and pathological processes via inhibiting target mRNA translation or promoting mRNA degradation. A number of studies have confirmed that both lncRNAs and miRNAs are closely associated with the development of cardiovascular diseases (CVDs), such as cardiac remodelling, heart failure, myocardial injury and arrhythmia, and that they act as biomarkers, potential therapeutic targets or strong indicators of prognosis; however, the underlying molecular mechanism has not been elucidated. Recently, emerging evidence showed that the novel regulatory mechanism underlying the crosstalk among lncRNAs, miRNAs and mRNAs plays a pivotal role in the pathophysiological processes of CVDs in response to stress stimuli. In this review, I comprehensively summarized the regulatory relationship of lncRNAs, miRNAs and mRNAs and highlighted the important role of the lncRNA‐miRNA‐mRNA axis in CVDs.

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“…Decreased PTEN expression has been reported in fibrotic diseases of the lungs, heart, skin as well as liver [14–18]. Specifically, deletion of the Pten gene in mice results in excess deposition of type I collagen, while PTEN overexpression can reverse chemical-induced liver fibrosis [19].…”

Section: Introductionmentioning

confidence: 99%

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

Kumar¹,

Raeman²,

Chopyk³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Adiponectin inhibits hepatic stellate cell (HSC) activation and subsequent development of liver fibrosis via multiple mechanisms. Phosphatase and tensin homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation, but its regulation by adiponectin is not fully understood. Here, we investigated the effect of adiponectin on PTEN in LX-2 cells, a human cell line and examined the underlying molecular mechanisms involved in adiponectin-mediated upregulation of PTEN activity during fibrosis. PTEN expression was found to be significantly reduced in the livers of mice treated with CCl4, whereas its expression was rescued by adiponectin treatment. The DNA methylation proteins DNMT1, DNMT3A, and DNMT3B are all highly expressed in activated primary HSCs compared to quiescent HSCs, and thus represent additional regulatory targets during liver fibrogenesis. Expression of DNMT proteins was significantly induced in the presence of fibrotic stimuli; however, only DNMT3B expression was reduced in the presence of adiponectin. Adiponectin-induced suppression of DNMT3B was found to be mediated by enhanced miR-29b expression. Furthermore, PTEN expression was significantly increased by overexpression of miR-29b, whereas its expression was markedly reduced by a miR-29b inhibitor in LX-2 cells. These findings suggest that adiponectin-induced upregulation of miR-29b can suppress DNMT3B transcription in LX-2 cells, thus resulting in reduced methylation of PTEN CpG islands and ultimately suppressing the PI3K/AKT pathway. Together, these data suggest a possible new explanation for the inhibitory effect of adiponectin on HSC activation and liver fibrogenesis.

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LncRNA GAS5 controls cardiac fibroblast activation and fibrosis by targeting miR-21 via PTEN/MMP-2 signaling pathway

Cited by 134 publications

References 20 publications

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway

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