MicroRNA-99b-3p promotes angiotensin II-induced cardiac fibrosis in mice by targeting GSK-3β

Yu, Youhui; Zhang, Yuhong; Ding, Yanqing; Bi, Xueying; Yuan, Jing; Zhou, Hang; Wang, Panxia; Zhang, Lili; Ye, Jiantao

doi:10.1038/s41401-020-0498-z

Cited by 27 publications

(17 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar regulatory mode has been observed for some other miRNAs, such as miR-21 and miR-324-3p (Thum et al, 2008;Zhang et al, 2019). Previously, we also revealed that miR-99b-3p attenuated GSK-3β protein expression but not its mRNA stability (Y. H. Yu et al, 2021). In line with these reports, our present study showed that VCP mRNA expression in NRCMs was intact following treatment with miR-339-5p mimic or inhibitor.…”

Section: Discussionsupporting

confidence: 84%

MiRNA‐339‐5p promotes isoproterenol‐induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling

Zhang

et al. 2021

Cell Biology International

Self Cite

View full text Add to dashboard Cite

MicroRNAs (miRNAs) regulate multiple biological processes and participate in various cardiovascular diseases. This study aims to investigate the role of miR-339-5p in cardiomyocyte hypertrophy and the involved mechanism. Neonatal rat cardiomyocytes (NRCMs) were cultured and stimulated with isoproterenol (ISO). The hypertrophic responses were monitored by measuring the cell surface area and expression of hypertrophic markers including β-myosin heavy chain (β-MHC) and atrial natriuretic factor (ANF). Bioinformatic prediction tools and dual-luciferase reporter assay were performed to identify the target gene of miR-339-5p. Quantitative realtime polymerase chain reaction and western blot analysis were used to determine the levels of miR-339-5p and its downstream effectors. Our data showed that miR-339-5p was upregulated during cardiomyocyte hypertrophy triggered by ISO. MiR-339-5p overexpression resulted in enlargement of cell size and increased the levels of hypertrophic markers. In contrast, inhibition of miR-339-5p significantly attenuated ISO-induced hypertrophic responses of NRCMs. Valosin-containing protein (VCP), a suppressor of cardiac hypertrophy via inhibiting mechanistic target of rapamycin (mTOR) signaling, was validated as a target of miR-339-5p. MiR-339-5p suppressed VCP protein expression, leading to elevated phosphorylation of mTOR and ribosomal protein S6 kinase (S6K). VCP depletion activated the mTOR/S6K cascade and could compromise the anti-hypertrophic effects of miR-339-5p inhibitor. Additionally, the hypertrophic responses caused by miR-339-5p was alleviated in the presence of mTOR inhibitor rapamycin. In conclusion, our research revealed that miR-339-5p promoted ISO-induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling, suggesting a promising therapeutic intervention by interfering miR-339-5p.

show abstract

Section: Discussionsupporting

confidence: 84%

MiRNA‐339‐5p promotes isoproterenol‐induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling

Zhang

et al. 2021

Cell Biology International

Self Cite

View full text Add to dashboard Cite

show abstract

“…GSK-3β is involved in the development of many cardiovascular diseases via multiple signal transduction pathways, such as Wnt/β-catenin ( Guo et al, 2012 ), TGF-β1-SMAD-3 ( Jope et al, 2007 ; Lal et al, 2014 ) and apoptosis ( Lal et al, 2015 ; Su et al, 2019 ). Recently, a study has revealed that targeting GSK-3β by microRNA-99b-3p promotes cardiac fibrosis ( Yu et al, 2020 ). Our present study showed that GSK-3β regulates myocardial fibrotic remodeling in MI via the activation of NLRP3 inflammasome ( Wang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting Glycogen Synthase Kinase 3 Beta Regulates CD47 Expression After Myocardial Infarction in Rats via the NF-κB Signaling Pathway

Wang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

The aim of this study was to investigate the effects of the GSK-3β/NF-κB pathway on integrin-associated protein (CD47) expression after myocardial infarction (MI) in rats. An MI Sprague Dawley rat model was established by ligating the left anterior descending coronary artery. The rats were divided into three groups: Sham, MI, and SB + MI (SB216763) groups. Immunohistochemistry was used to observe the changes in cardiac morphology. A significant reduction in the sizes of fibrotic scars was observed in the SB + MI group compared to that in the MI group. SB216763 decreased the mRNA and protein expression of CD47 and NF-κB during MI. Primary rat cardiomyocytes (RCMs) and the H9c2 cell line were used to establish in vitro hypoxia models. Quantitative real-time PCR and western blotting analyses were conducted to detect mRNA and protein expression levels of CD47 and NF-κB and apoptosis-related proteins, respectively. Apoptosis of hypoxic cells was assessed using flow cytometry. SB216763 reduced the protein expression of CD47 and NF-κB in RCMs and H9c2 cells under hypoxic conditions for 12 h, and alleviated hypoxia-induced apoptosis. SN50 (an NF-κB inhibitor) also decreased CD47 protein expression in RCMs and H9c2 cells under hypoxic conditions for 12 h and protected cells from apoptosis. GSK-3β upregulates CD47 expression in cardiac tissues after MI by activating NF-κB, which in turn leads to myocardial cell damage and apoptosis.

show abstract

“…Next, the cells were treated with 100 ng of Ang II, 19 and further with EVs (50 μg/ml), 18 pGMLV‐MIAT, si‐MIAT, pGMLV‐CXCL10 (CXCL10 overexpression plasmids), miR‐485‐5p mimic, pGMLV‐MIAT + miR‐485‐5p mimic, EVs + si‐CXCL10, pGMLV‐MIAT + si‐CXCL10, pGMLV‐Vector, si‐NC, mimic NC, pGMLV‐MIAT + mimic NC, EVs + si‐NC, or pGMLV‐MIAT + si‐NC, respectively. At 48 h posttransfection, the following assays were implemented.…”

Section: Methodsmentioning

confidence: 99%

Serum extracellular vesicles containing MIAT induces atrial fibrosis, inflammation and oxidative stress to promote atrial remodeling and atrial fibrillation via blockade of miR‐485‐5p‐mediated CXCL10 inhibition

Chen

et al. 2021

Clinical & Translational Med

View full text Add to dashboard Cite

Background Atrial fibrillation (AF), a supraventricular arrhythmia that impairs cardiac function, is a main source of morbidity and mortality. Serum‐derived extracellular vesicles (EVs) have been identified to carry potential biomarker or target for the diagnosis and treatment of AF. We intended to dissect out the role of lncRNA MIAT enriched in serum‐derived EVs in AF. Methods MIAT expression was quantified in EVs isolated from serum samples of AF patients. Mouse and cell models of AF were developed after angiotensin II (Ang II) induction. Relationship between MIAT, miR‐485‐5p, and CXCL10 was identified. Ectopic expression and depletion assays were implemented in Ang II‐treated mice or HL‐1 cells, or those co‐cultured with serum‐derived EVs to explore the roles of EV‐carried MIAT. Results MIAT was upregulated in EVs from serum samples of AF patients. Further analysis indicated that MIAT enriched in serum‐derived EVs promoted atrial fibrosis, inflammation and oxidative stress, and aggravated the atrial remodeling and resultant AF. Mechanistically, MIAT bound to miR‐485‐5p and weakened its inhibitory role on the target CXCL10, which was responsible for the role of serum‐derived EV containing MIAT in cellular fibrosis, oxidative stress and inflammation, and atrial remodeling in vivo. Conclusions In conclusion, serum‐derived EV containing MIAT facilitates atrial remodeling and exacerbates the AF by abolishing the miR‐485‐5p‐mediated CXCL10 inhibition. This finding aids in the deeper understanding about the pathophysiology of AF.

show abstract

MicroRNA-99b-3p promotes angiotensin II-induced cardiac fibrosis in mice by targeting GSK-3β

Cited by 27 publications

References 50 publications

MiRNA‐339‐5p promotes isoproterenol‐induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling

MiRNA‐339‐5p promotes isoproterenol‐induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling

Targeting Glycogen Synthase Kinase 3 Beta Regulates CD47 Expression After Myocardial Infarction in Rats via the NF-κB Signaling Pathway

Serum extracellular vesicles containing MIAT induces atrial fibrosis, inflammation and oxidative stress to promote atrial remodeling and atrial fibrillation via blockade of miR‐485‐5p‐mediated CXCL10 inhibition

Contact Info

Product

Resources

About