LncRNA AZIN1-AS1 ameliorates myocardial ischemia–reperfusion injury by targeting miR-6838-5p/WNT3A axis to activate Wnt-β/catenin signaling pathway

Zhang, Guoming; Ding, Licheng; Sun, Guangfeng; Liu, Zhixian; Ou, Weimei; Wang, Bin; Sun, Yuhao

doi:10.1007/s11626-022-00646-1

Cited by 11 publications

(8 citation statements)

References 35 publications

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“…In recent years, the importance of the Wnt/β‐catenin signaling in the pathogenesis of AMI has become increasingly clear (Q. Wang, Ma, et al, 2021; Yang et al, 2017; G. Zhang, Ding, et al, 2022). Hence, we focused on the Wnt family‐related genes in this study.…”

Section: Resultsmentioning

confidence: 99%

“…Recent research has indicated the vital role of the Wnt/β-catenin signaling pathway in the development of AMI (Q. Wang, Ma, et al, 2021;G. Zhang, Ding, et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Recent research has indicated the vital role of the Wnt/β‐catenin signaling pathway in the development of AMI (Q. Wang, Ma, et al, 2021; G. Zhang, Ding, et al, 2022). Furthermore, it has been reported that inhibitors of the Wnt pathway might contribute to cardiac regeneration after AMI (Yang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of long noncoding RNA MIAT attenuates hypoxia‐induced cardiomyocyte injury by regulating the miR‐488‐3p/Wnt/β‐catenin pathway

Zhang

et al. 2022

Cell Biology International

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Dysfunction of cardiomyocytes contributes to the development of acute myocardial infarction (AMI). Nonetheless, the regulatory mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in cardiomyocyte injury remains largely unclear. The cardiomyocyte injury was assessed via cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and flow cytometry, respectively. The levels of MIAT, microRNA (miR)-488-3p, and Wnt5a were detected via quantitative real-time polymerase chain reaction and Western blot.After bioinformatical analysis, the binding between miR-488-3p and MIAT or Wnt5a was confirmed via dual-luciferase reporter, RNA immunoprecipitation, and RNA pulldown assays. Our results showed that MIAT expression was increased in AC16 cells after hypoxia treatment. Silencing of MIAT alleviated hypoxia-induced viability reduction, apoptosis increase, and Wnt/β-catenin pathway activation. MIAT directly targeted miR-488-3p. MiR-488-3p might repress hypoxia-induced cardiomyocyte injury, and its knockdown reversed the effect of MIAT depletion on cardiomyocyte injury. Wnt5a was validated as a target of miR-488-3p. Wnt5a expression restoration attenuated the influence of MIAT knockdown on hypoxia-triggered cardiomyocyte injury. Our findings demonstrated that downregulation of MIAT might mitigate hypoxia-induced cardiomyocyte injury partly through miR-488-3p mediated Wnt/β-catenin pathway.

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Section: Resultsmentioning

confidence: 99%

“…Recent research has indicated the vital role of the Wnt/β-catenin signaling pathway in the development of AMI (Q. Wang, Ma, et al, 2021;G. Zhang, Ding, et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of long noncoding RNA MIAT attenuates hypoxia‐induced cardiomyocyte injury by regulating the miR‐488‐3p/Wnt/β‐catenin pathway

Zhang

et al. 2022

Cell Biology International

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“…However, a few studies have also demonstrated that activating the Wnt3/β‐catenin pathway inhibits cardiomyocyte apoptosis and protects against myocardial injury after MI. 50 , 51 , 52 These contradictory results may be partly due to the different models and diverse experimental times used for in vivo and in vitro studies, because Wnt signaling is a highly time‐ and context‐dependent pathway. 41 In our study, we found that PI16 inhibited OGD‐induced NRCM apoptosis by downregulating Wnt3a/β‐catenin signaling, and that recombinant Wnt3a reversed the inhibitory effect of PI16 on cardiomyocyte apoptosis, suggesting that PI16 alleviated myocardial apoptosis by suppressing the Wnt3a/β‐catenin pathway.…”

Section: Discussionmentioning

confidence: 99%

Peptidase Inhibitor 16 Attenuates Left Ventricular Injury and Remodeling After Myocardial Infarction by Inhibiting the HDAC1‐Wnt3a‐β‐Catenin Signaling Axis

Wang

Lü

et al. 2023

JAHA

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Background Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms. Methods and Results PI16 levels after MI were measured by enzyme‐linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts. PI16 gain‐ and loss‐of‐function experiments were used to investigate the potential role of PI16 after MI. In vitro, PI16 overexpression inhibited oxygen–glucose deprivation–induced apoptosis in neonatal rat cardiomyocytes, whereas knockdown of PI16 exacerbated neonatal rat cardiomyocyte apoptosis. In vivo, left anterior descending coronary artery ligation was performed on PI16 transgenic mice, PI16 knockout mice, and their littermates. PI16 transgenic mice showed decreased cardiomyocyte apoptosis at 24 hours after MI and improved left ventricular remodeling at 28 days after MI. Conversely, PI16 knockout mice showed aggravated infract size and remodeling. Mechanistically, PI16 downregulated Wnt3a (wingless‐type MMTV integration site family, member 3a)/β‐catenin pathways, and the antiapoptotic role of PI16 was reversed by recombinant Wnt3a in oxygen–glucose deprivation–induced neonatal rat cardiomyocytes. PI16 also inhibited HDAC1 (class I histone deacetylase) expression, and overexpression HDAC1 abolished the inhibition of apoptosis and Wnt signaling of PI16. Conclusions In summary, PI16 protects against cardiomyocyte apoptosis and left ventricular remodeling after MI through the HDAC1‐Wnt3a‐β‐catenin axis.

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“… 93 Zhang et al found that AZIN1-AS1 was significantly downregulated and miR-6838-5p was significantly upregulated in the myocardium of myocardial I/R rats and H/R H9C2 cells; this dysregulation ultimately led to the downregulation of Wnt3a expression, which in turn inhibited Wnt/β-catenin signaling and induced apoptosis. 94 Additionally, Cui et al established that the inhibition of Wnt/β-catenin signaling in I/R rat myocardium and H/R H9c2 cells, initiated by the downregulation of Wnt3a, promoted cardiomyocyte apoptosis. 95 …”

Section: Wnt Pathways and Organ I/r Injurymentioning

confidence: 99%

Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets

Zhang,

Liu,

Meng

et al. 2024

Sig Transduct Target Ther

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Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic interventions. The Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system of signaling pathways involved in I/R injury. This review article elucidates the underlying mechanisms involved in Wnt signaling, as well as the complex interplay between Wnt and other pathways, including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-β, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca2+-Activin A, Hippo-Yes-associated protein, toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β, and hepatocyte growth factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, including apoptosis, the inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, and blood-brain barrier damage during I/R injury. Our comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery, while activation of the non-canonical Wnt pathways exacerbates injury. Moreover, we explore novel therapeutic approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, and clinical trials. The objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction, to facilitate the development of innovative therapeutic agents for I/R injury.

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LncRNA AZIN1-AS1 ameliorates myocardial ischemia–reperfusion injury by targeting miR-6838-5p/WNT3A axis to activate Wnt-β/catenin signaling pathway

Cited by 11 publications

References 35 publications

Knockdown of long noncoding RNA MIAT attenuates hypoxia‐induced cardiomyocyte injury by regulating the miR‐488‐3p/Wnt/β‐catenin pathway

Knockdown of long noncoding RNA MIAT attenuates hypoxia‐induced cardiomyocyte injury by regulating the miR‐488‐3p/Wnt/β‐catenin pathway

Peptidase Inhibitor 16 Attenuates Left Ventricular Injury and Remodeling After Myocardial Infarction by Inhibiting the HDAC1‐Wnt3a‐β‐Catenin Signaling Axis

Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets

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