P2X7 receptor is involved in lung injuries induced by ischemia-reperfusion in pulmonary arterial hypertension rats

Duan, Lian; Hu, Guo‐Huang; Li, Yi-jin; Zhang, Chengliang; Jiang, Meng

doi:10.1016/j.molimm.2018.07.027

Cited by 21 publications

(13 citation statements)

References 50 publications

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“…In a mouse model of acetaminophen-(APAP-) induced hepatotoxicity, a combination of celastrol and BBG prevented the hepatic antioxidant consumption (decreased superoxide dismutase and glutathione) and hepatocellular injury [32]. Elsewhere, administration of BBG decreased superoxide dismutase (SOD), malondialdehyde (MDA), TNF-α, and IL-1β concentration in pulmonary arterial hypertension (PAH) and ischemia-reperfusion-(IR-) induced lung models [33]. In our TAC mouse model, BBG affected several pathways controlled by P2X7R.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of P2X7 Purinergic Receptor Ameliorates Cardiac Fibrosis by Suppressing NLRP3/IL-1β Pathway

Zhou

Tian

Quan

et al. 2020

Oxidative Medicine and Cellular Longevity

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P2X7 purinergic receptor (P2X7R) has been implicated in several cardiovascular diseases. However, whether it regulates cardiac fibrosis remains elusive. Herein, its involvement in the development of cardiac fibrosis was examined using a transverse aortic constriction (TAC) mice model and cardiac fibroblasts (CFs) hyperstimulated by TGF-β1 for 48 hours. Results showed that TAC and TGF-β1 treatment increased the expression of P2X7R. Silencing of P2X7R expression with siP2X7R ameliorated TGF-β1 effects on fibroblasts activation. Similarly, P2X7R inhibition by Brilliant Blue G (BBG) reduced mRNA and protein levels of profibrosis markers, while the P2X7R agonist BzATP accelerated the TGF-β1-induced CFs activation. Moreover, it was found that TGF-β1-induced CFs activation was mediated by the NLRP3/IL-1β inflammasome pathway. BBG or siP2X7R treatment suppressed NLRP3/IL-1β pathway signaling. In vivo, BBG significantly alleviated TAC-induced cardiac fibrosis, cardiac dysfunction, and NLRP3/IL-1β activation. Collectively, our findings imply that suppressing P2X7R may limit cardiac fibrosis and abnormal activation of CFs.

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Section: Discussionmentioning

confidence: 99%

Inhibition of P2X7 Purinergic Receptor Ameliorates Cardiac Fibrosis by Suppressing NLRP3/IL-1β Pathway

Zhou

Tian

Quan

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…It was already reported its capacity to modulate acute and chronic infection [81,82], inflammatory diseases [82], sepsis [83,84], neuropathic pain [85], and T-cell activation [86]. In addition, P2X7 receptor expression deletion appears to be beneficial in case of acute lung injury, asthma, lung inflammation, and fibrosis [87][88][89][90][91]. Remarkably, P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke [21,[92][93][94][95], as further discussed.…”

Section: P2x7 Receptor Role In Inflammationmentioning

confidence: 99%

“…The massive ATP release following lung mononuclear phagocytes invasion by SARS-CoV-2 can activate P2X7 receptors of antigen-presenting cells and macrophages, increasing cytokine, chemokine and ATP secretion [16]. In addition, P2X7 receptor knockout mice submitted to a model of lung fibrosis revealed reduced infiltration of inflammatory cells, cytokine release, apoptosis, and fibrosis, while P2X7 receptor agonists increased these deleterious processes [88,107].…”

Section: P2x7 Receptor Role In Inflammationmentioning

confidence: 99%

“…Since the P2X7 receptor is also involved in lung damage [87][88][89], neurodegenerative and psychiatric disorders [92,95,118], the hypothesis is reasonable that inhibition of this receptor might decrease pathological traits mediated by the RAAS pressor axis and protect against brain and lung injury in COVID-19 patients. Indeed, evidence demonstrates that P2X7 receptor blockade prevents Ang IItriggered pro-inflammatory responses [119].…”

Section: P2x7 Receptors and The Renin-angiotensin Systemmentioning

confidence: 99%

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Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

et al. 2020

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Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called “cytokine storm”. Both pro-inflammatory factors and viruses may cross the blood–brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson’s and Alzheimer’s disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.

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“…GTPase catalyzes GTP to GDP and then to ATP. Nevertheless, the increase of ATP is obviously pernicious factors to PAH [32][33][34][35]. Furthermore, a few complexes gradually formed at this stage, like "Ubiquitin E3 ligase (SIAH1, SIP, SKP1A, TBL1X)".…”

Section: Discussionmentioning

confidence: 99%

The prediction of the crucial regulatory factors and functional analysis in pulmonary arterial hypertension by re-annotation

Li²,

et al. 2019

Preprint

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Background Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance, which increases the right ventricular load and eventually leads to right ventricular failure and death. Recent theoretical developments have revealed that quiet a few lncRNAs played an important role in the development of pulmonary vascular diseases, such as H19, tcons_00034812. However, the mechanism of mRNA regulated by lncRNA in the PAH remained unclear. Results In our study, we re-annotated Affymetrix Murine Genome array to Human reference genome(hg38) by using the data from GENCODE database, in the light of lncRNA and mRNA. We screened differentially expressed lncRNA/mRNA between PAH samples and normal samples. Then we constructed PAH related lncRNA/mRNA co-expression network and analyzed topological properties of the network. We excavated the modules by the WGCNA R package. The genes in the modules excavated are used for enrichment analysis of functions and pathways. Finally, 8 functional modules were identified as pathogenic modules, providing new ideas for understanding the potential mechanisms of PAH. Conclusions We generated a new strategy to do research on pulmonary arterial hypertension. The pathogenic modules played an important role and could offer new therapeutic targets for pulmonary arterial hypertension mechanism research.

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P2X7 receptor is involved in lung injuries induced by ischemia-reperfusion in pulmonary arterial hypertension rats

Cited by 21 publications

References 50 publications

Inhibition of P2X7 Purinergic Receptor Ameliorates Cardiac Fibrosis by Suppressing NLRP3/IL-1β Pathway

Inhibition of P2X7 Purinergic Receptor Ameliorates Cardiac Fibrosis by Suppressing NLRP3/IL-1β Pathway

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

The prediction of the crucial regulatory factors and functional analysis in pulmonary arterial hypertension by re-annotation

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