CBL aggravates Ang II-induced cardiac hypertrophy via the VHL/HIF-1α pathway

Yang, Yuting; Zou, Pengtao; He, Lin; Shao, Jun; Tang, Yanhua; Li, Juxiang

doi:10.1016/j.yexcr.2021.112730

Cited by 7 publications

(9 citation statements)

References 24 publications

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“…29 Importantly, Yang et al previously reported that CBL exacerbated myocardial hypertrophy via direct interaction with VHL and degradation of VHL by enhancing the ubiquitination level. 30 However, the possible link between CBL and βcatenin in myocardial I/R injury remains unknown. We demonstrated that CBL is involved in βcatenin-dependent myocardial I/R injury pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, CBL was revealed to facilitate JAK2 ubiquitination to decrease JAK2 and STAT4 expression, thereby ameliorating endothelial dysfunction in diabetic models 29 . Importantly, Yang et al previously reported that CBL exacerbated myocardial hypertrophy via direct interaction with VHL and degradation of VHL by enhancing the ubiquitination level 30 . However, the possible link between CBL and β‐catenin in myocardial I/R injury remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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FTO represses NLRP3‐mediated pyroptosis and alleviates myocardial ischemia–reperfusion injury via inhibiting CBL‐mediated ubiquitination and degradation of β‐catenin

et al. 2023

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Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygenglucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1β production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and βcatenin and βcatenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and βcatenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/β-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed βcatenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of βcatenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of βcatenin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

FTO represses NLRP3‐mediated pyroptosis and alleviates myocardial ischemia–reperfusion injury via inhibiting CBL‐mediated ubiquitination and degradation of β‐catenin

et al. 2023

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“…The heart function was assessed using a two-dimensional echocardiography system (Vevo 2100; Visual Sonics, Toronto, ON, Canada) on an MS250 transducer (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Left ventricular ejection fraction (LVEF, EF%), left ventricular fractional shortening (LVFS, FS%), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic dimension (LVEDD) and heart rate (HR) were all calculated.…”

Section: Echocardiography Assessing Cardiac Functionsmentioning

confidence: 99%

Ectopic Acsl6 Overexpression Partially Improves Isoproterenol-Induced Cardiac Hypertrophy In Vivo and Cardiomyocyte Hypertrophy In Vitro

Liu

Long

et al. 2022

Journal of Cardiovascular Pharmacology

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The increase in cardiac myocyte size is a critical issue in cardiac hypertrophy development. In this study, 61 differentially expressed genes between hypertrophic rats and normal controls were enriched in the positive modulation of fatty acid uptake, fatty acid metabolism and degradation, cardiac conduction, and the oxidation of carbohydrates and other processes. Acsl6 was significantly downregulated in hypertrophic rat and mouse hearts according to online data. Based on the experimental data, Acsl6 was underexpressed in ISO-induced cardiac hypertrophy mouse model and isoproterenol (ISO)-induced cardiomyocyte hypertrophy cell model. In vivo, Acsl6 overexpression partially attenuated ISO-induced increases in the cross-sectional area and cardiac hypertrophy, elevated hypertrophic markers, and caused impairment of cardiac function. In vitro, Acsl6 overexpression partially attenuated ISOinduced cardiomyocyte hypertrophy and increased hypertrophic markers. Conclusively, Ascl6 is downregulated in ISO-induced cardiac hypertrophy mouse model and ISO-induced cardiomyocyte hypertrophy cell model. Acsl6 overexpression could partially improve cardiac hypertrophy in vivo and cardiomyocyte hypertrophy in vitro, possibly through the regulation of HIF-1a/Hippo pathway.

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“…The specific mechanism is: under normoxia conditions, HIF1α undergoes hydroxylation under the action of prolyl hydroxylase (PHD), and it is recognized and bound by the von Hippel-Lindau tumor suppressor (VHL), when the HIF1α binds to VHL, then it is ubiquitinated and degraded. Under hypoxia, the oxygen-dependent proline hydroxylation reaction is blocked due to the inactivation of PHD, HIF1α is not degraded, and the accumulated HIF1α enters the nucleus and combines with HIF1β to form a dimer, and the dimer regulates the expression of related genes under hypoxic conditions with the participation of transcriptional co-activators such as histone acetyltransferase p300, and finally realizes the adaptation of cells to hypoxia conditions [ 2 , 3 , 4 , 5 , 6 ] ( Figure 1 ). HIF2 is composed of HIF2α and HIF2β.…”

Section: Introductionmentioning

confidence: 99%

HIF in Gastric Cancer: Regulation and Therapeutic Target

Guan

Yang

et al. 2022

Molecules

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HIF means hypoxia-inducible factor gene family, and it could regulate various biological processes, including tumor development. In 2021, the FDA approved the new drug Welireg for targeting HIF-2a, and it is mainly used to treat von Hippel-Lindau syndrome, which demonstrated its good prospects in tumor therapy. As the fourth deadliest cancer worldwide, gastric cancer endangers the health of people all across the world. Currently, there are various treatment methods for patients with gastric cancer, but the five-year survival rate of patients with advanced gastric cancer is still not high. Therefore, here we reviewed the regulatory role and target role of HIF in gastric cancer, and provided some references for the treatment of gastric cancer.

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CBL aggravates Ang II-induced cardiac hypertrophy via the VHL/HIF-1α pathway

Cited by 7 publications

References 24 publications

FTO represses NLRP3‐mediated pyroptosis and alleviates myocardial ischemia–reperfusion injury via inhibiting CBL‐mediated ubiquitination and degradation of β‐catenin

FTO represses NLRP3‐mediated pyroptosis and alleviates myocardial ischemia–reperfusion injury via inhibiting CBL‐mediated ubiquitination and degradation of β‐catenin

Ectopic Acsl6 Overexpression Partially Improves Isoproterenol-Induced Cardiac Hypertrophy In Vivo and Cardiomyocyte Hypertrophy In Vitro

HIF in Gastric Cancer: Regulation and Therapeutic Target

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