TLR3 Mediates Repair and Regeneration of Damaged Neonatal Heart through Glycolysis Dependent YAP1 Regulated miR-152 Expression

Wang, Xiaohui; Ha, Tuanzhu; Liu, Li; Hu, Yuanyang; Kao, Race L.; Kalbfleisch, John H.; Williams, David L.; Li, Chuanfu

doi:10.1038/s41418-017-0036-9

Cited by 73 publications

(82 citation statements)

References 49 publications

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“…To further support the protective action of resveratrol on HR injured N2a cells, a TUNEL assay was performed to quantify cell death . As shown in Figure C and D, compared to the control group, HR injury increased the ratio of TUNEL‐positive cells, and this effect was reversed by high dose resveratrol.…”

Section: Resultsmentioning

confidence: 89%

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

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Summary The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.

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Section: Resultsmentioning

confidence: 89%

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

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“…To investigate the mechanisms by which lactate induced YAP phosphorylation and inactivation, we examined the effect of lactate on AMPK activation. We have previously shown that AMPK activation resulted in YAP phosphorylation and inactivation ( 34 ). Figure 4B shows that treatment of macrophages with lactate significantly increased AMPK phosphorylation.…”

Section: Resultsmentioning

confidence: 99%

Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB Activation via GPR81-Mediated Signaling

et al. 2020

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Recent evidence from cancer research indicates that lactate exerts a suppressive effect on innate immune responses in cancer. This study investigated the mechanisms by which lactate suppresses macrophage pro-inflammatory responses. Macrophages [Raw 264.7 and bone marrow derived macrophages (BMDMs)] were treated with LPS in the presence or absence of lactate. Pro-inflammatory cytokines, NF-κB and YAP activation and nuclear translocation were examined. Our results show that lactate significantly attenuates LPS stimulated macrophage TNF-α and IL-6 production. Lactate also suppresses LPS stimulated macrophage NF-κB and YAP activation and nuclear translocation in macrophages. Interestingly, YAP activation and nuclear translocation are required for LPS stimulated macrophage NF-κB activation and TNFα production. Importantly, lactate suppressed YAP activation and nuclear translocation is mediated by GPR81 dependent AMKP and LATS activation which phosphorylates YAP, resulting in YAP inactivation. Finally, we demonstrated that LPS stimulation induces an interaction between YAP and NF-κB subunit p65, while lactate decreases the interaction of YAP and NF-κB, thus suppressing LPS induced pro-inflammatory cytokine production. Our study demonstrates that lactate exerts a previously unknown role in the suppression of macrophage pro-inflammatory cytokine production via GPR81 mediated YAP inactivation, resulting in disruption of YAP and NF-κB interaction and nuclear translocation in macrophages.

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“…Nucleotide supplementation can partially rescue the yap −/− phenotype (Cox et al, 2018). In vitro and in vivo assessment of neonatal cardiomyocyte repair and regeneration revealed that YAP1 was activated when glycolytic metabolism was enhanced, whereas inhibition of glycolysis suppressed YAP activation (Wang et al, 2018). O ‐GlcNAcylation is a specific type of post‐translational modification catalyzed by O ‐GlcNAc transferase (OGT), resulting in the transfer of O ‐linked β ‐ N ‐acetylglucosamine (O‐GlcNAc) to the hydroxyl group of serine (Ser) or threonine (Thr) residues in the target protein.…”

Section: Metabolic Regulation Of Yap Nuclear Transportmentioning

confidence: 99%

YAP nuclear‐cytoplasmic translocation is regulated by mechanical signaling, protein modification, and metabolism

Zou

Feng

et al. 2020

Cell Biology International

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Nuclear‐cytoplasmic transport is necessary for the biological function of nuclear proteins. The mechanism underlying this process is very complex and has been a subject of intense research. Yes‐associated protein (YAP), a Hippo signaling pathway effector, localizes to both the cytoplasm and the nucleus and can influence cell proliferation, stem cell status, and tissue homeostasis. Recent studies have focused on the significance of YAP distribution between the nucleus and the cytoplasm in disease, but it remains unclear how this dynamic process is regulated. In this review, we discuss YAP nuclear‐cytoplasmic transport under different physiological and pathological conditions in terms of mechanical signaling, protein modification, and metabolism. Understanding the mechanisms underlying nuclear‐cytoplasmic YAP transport mechanism under different physiological and pathological conditions may help identify important targets for disease treatment.

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TLR3 Mediates Repair and Regeneration of Damaged Neonatal Heart through Glycolysis Dependent YAP1 Regulated miR-152 Expression

Cited by 73 publications

References 49 publications

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB Activation via GPR81-Mediated Signaling

YAP nuclear‐cytoplasmic translocation is regulated by mechanical signaling, protein modification, and metabolism

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