The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest

Liu, Wenxun; Ye, Qingshan; Xi, Wenhua; Li, Yan; Zhou, Xin; Wang, Yun; Ye, Zhenhai; Hai, Kerong

doi:10.1016/j.intimp.2021.107689

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Therefore, we hypothesized that PTN may be related to WMI pathogenesis and has the potential to treat WMI. We first detected the expression of PTN after WMI and found that the expression of endogenous PTN was significantly reduced after WMI, consistent with the results of Liu et al 46 Hence, in our study, we supplemented PTN and investigated the effect of PTN in rats with WMI.…”

Section: Discussionsupporting

confidence: 90%

“…These studies suggest that PTN promotes OL differentiation and myelination in vitro. 16 Additionally, Liu et al 46 showed that the expression of endogenous PTN in brain tissue was decreased in rats with cerebral ischemia-reperfusion injury in a cardiopulmonary resuscitation model. Therefore, we hypothesized that PTN may be related to WMI pathogenesis and has the potential to treat WMI.…”

Section: Discussionmentioning

confidence: 99%

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Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

Qiu

Zhou

et al. 2023

The FASEB Journal

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Brain white matter injury (WMI) is a serious disease of the central nervous system. Pleiotrophin (PTN) promotes the differentiation and myelination of oligodendrocytes (OLs) in vitro. However, the role of PTN in WMI remains unknown. Therefore, this study aimed to investigate the neuroprotective role and potential mechanisms of PTN function in neonatal rats with WMI. The PTN and mammalian target of rapamycin (mTOR) inhibitor everolimus was used to treat a WMI model in postnatal day 3 Sprague–Dawley rats, in which the right common carotid arteries of these rats were isolated, ligated, and exposed to a hypoxic environment (6% O2 + 94% N2) for 2 h. OL differentiation and myelination, as well as the spatial learning and memory abilities of the rats were evaluated to examine the effects of PTN. Two proteins of the mTOR signaling pathway, YingYang1 (YY1) and inhibitor of DNA binding 4 (Id4), were detected and were used to explore the potential mechanisms of PTN in rat WMI experiment and oxygen glucose deprivation (OGD) model. We found that the differentiation and myelination of OLs were impaired after WMI. PTN administration rescued this injury by activating mTOR/YY1 and inhibiting Id4. Everolimus administration inhibited mTOR/YY1 and activated Id4, which blocked the neuroprotective role of PTN in WMI. PTN plays a neuroprotective role in neonatal rats with WMI, which could be involved in the mTOR/YY1/Id4 signaling pathway.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

Qiu

Zhou

et al. 2023

The FASEB Journal

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“…Recent studies have reported that activation of the Erk signaling cascade by a number of different agents can exert significant neuroprotection against ischemic injury in vitro and in vivo. Liu et al reported that heparin activation of the Erk-CREB-PTN-syndecan-3 cascade attenuated ischemia/reperfusion neuronal injury [ 63 ]. Zhao et al demonstrated that cytosine inhibits cerebral ischemia/reperfusion injury in mice by activating the NR2B-ERK-CREB cascade [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury

Liu,

Shi,

et al. 2023

Cell Death Dis

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The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and β-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.

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“…To avoid the adverse effects on the process of nerve regeneration, some drugs or non-drug therapies can be used to save the over-inhibition of ERK/CREB pathway by analgesics. The heparin can promote nerve regeneration by up-regulating the expression of ERK/CREB pathway in the brain of rats during the rehabilitation process after cerebral ischemia and reperfusion injury, and then mediate the multiple effect protein (PTN)/ syndecan-3 pathway ( Liu W. et al, 2021 ). The Chinese Medicine ingredient panaxydol can induce axonal growth and play a role in nerve regeneration by activating ERK/CREB pathway ( Li et al, 2018 ).…”

Section: Adverse Effects Of Analgesics Related To Nervous Systemmentioning

confidence: 99%

Mechanism of ERK/CREB pathway in pain and analgesia

Zhen

Wang

et al. 2023

Front. Mol. Neurosci.

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Research has long centered on the pathophysiology of pain. The Transient Receiver Potential (TRP) protein family is well known for its function in the pathophysiology of pain, and extensive study has been done in this area. One of the significant mechanisms of pain etiology and analgesia that lacks a systematic synthesis and review is the ERK/CREB (Extracellular Signal-Regulated Kinase/CAMP Response Element Binding Protein) pathway. The ERK/CREB pathway-targeting analgesics may also cause a variety of adverse effects that call for specialized medical care. In this review, we systematically compiled the mechanism of the ERK/CREB pathway in the process of pain and analgesia, as well as the potential adverse effects on the nervous system brought on by the inhibition of the ERK/CREB pathway in analgesic drugs, and we suggested the corresponding solutions.

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The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest

Cited by 10 publications

References 40 publications

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway

Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury

Mechanism of ERK/CREB pathway in pain and analgesia

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