Ask about this productRelated genes to: P2RX7 Blocking Peptide
- Gene:
- P2RX7 NIH gene
- Name:
- purinergic receptor P2X 7
- Previous symbol:
- -
- Synonyms:
- P2X7, MGC20089
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-09
- Date modifiied:
- 2016-10-05
Related products to: P2RX7 Blocking Peptide
Related articles to: P2RX7 Blocking Peptide
- Bone cells are known to express multiple purinergic receptors. These are involved in various aspects of bone physiology depending on the cell type and receptor involved, both in normal and disease states, with extracellular ATP being particularly abundant in the bone microenvironment. The P2X7R subtype has been the subject of in-depth research in bone homeostasis. Different splice isoforms and single nucleotide polymorphisms (SNPs) have been discovered in the P2RX7 gene, these have functional implications on the receptor, conferring both gain of function (GOF) and loss of function (LOF), with consequences for bone phenotype, turnover and mass. We examined the full length P2RX7A, truncated P2RX7B, their co-expression and different receptor SNPs. The SNPs included the c.489C > T variant (p.His155Tyr) GOF, c.946G > A (p.Arg307Gln) LOF and c.1513A > C (p.Glu496Ala) LOF. The effect of these isoforms and SNPs on the normal cellular behaviour of the TE85 osteoblastic cell line were measured for intracellular calcium uptake, pore formation, cell proliferation, Alkaline phosphatase (ALP) activity, mineralisation, and changes in osteogenic gene expression. The results demonstrate that transfection of P2RX7 isoforms and SNP variants influenced several important bone processes. Compared to TE85 cells all isoform variants had an increased calcium response with only the co-transfected P2RX7AB having pore formation. This variant also had the highest mineralisation and ALP activity but was the least proliferative. Of the co-transfected SNP variants only the TE85 + P2RX7B + 155Y GOF cell line had both pore formation and an increased calcium response. Mineralisation was lower in all SNP cell lines as was ALP activity, however, proliferation was increased. Mechanistically, gene expression arrays showed that Nuclear Factor of Activated T-cells 1 (NFATc1) increased in the highly proliferative cell variants. Osteogenic genes such as Bone morphogenetic protein 2 (BMP2), ALP and collagen type I alpha 1 chain (COL1A1) were increased in the cell variants that had high mineralisation and ALP activity, and were decreased in the highly proliferative variants, demonstrating multiple bone phenotypes depending on GOF or LOF. In conclusion, this study extends our knowledge into the role of the P2X7R in maintaining bone homeostasis and provides assessment of P2RX7 polymorphisms in osteoblasts. In future this could help to identify associations between specific variants and increased/reduced bone mineral density or accelerated bone loss/fracture risk in a number of bone related conditions. - Source: PubMed
Publication date: 2026/06/27
Tattersall LukeWang QiguangGiuliani Anna LisaAdinolfi ElenaGartland Alison - Zoonotic tuberculosis (zoonotic TB) caused by () accounts for up to 10% of human tuberculosis cases in some regions, but the underlying pathogenic mechanisms remain incompletely understood, especially those involved in cellular pyroptosis. This study aimed to explore the regulatory roles of non-coding RNA (ncRNA) in the pyroptosis of human monocytic THP-1 cells induced by infection. An in vitro pyroptosis model was established by infecting THP-1 cells with , followed by whole-transcriptome sequencing to identify differentially expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). Bioinformatics analysis was performed to construct an lncRNA-miRNA-mRNA regulatory network associated with infection-induced pyroptosis; in addition, overexpression, knockdown, and dual-luciferase reporter assays and quantitative PCR were conducted to verify the interactions and functions of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-20b-5p, and purinergic receptor P2X7 (P2RX7). Transcriptome analysis detected 741 mRNAs, 1049 lncRNAs, 25 circRNAs, and 40 miRNAs with significant differential expression in infected THP-1 cells. Specifically, MALAT1 and P2RX7 were upregulated, while miR-20b-5p was downregulated after infection. Knockdown of MALAT1 or P2RX7 and overexpression of miR-20b-5p relieved -induced pyroptosis in THP-1 cells. Mechanistically, MALAT1 targeted miR-20b-5p, which directly targeted P2RX7, and overexpression of miR-20b-5p partially reversed P2RX7 upregulation mediated by MALAT1 overexpression. This study provides a transcriptomic characterization of -induced pyroptosis in THP-1 cells and supports the MALAT1-miR-20b-5p-P2RX7 axis as a potential regulatory mechanism involved in this process, offering initial molecular insights into the pathogenesis of zoonotic TB. - Source: PubMed
Publication date: 2026/05/31
Tian TianWang XiaonanZhu YananWang QiZheng WeiShi KunDu Rui - Ischemic stroke remains a leading cause of death and long-term disability, yet effective treatments that promote recovery beyond the acute phase are lacking. Neuregulin-1 (NRG-1) has shown potent neuroprotective and anti-inflammatory properties in preclinical stroke models, with evidence of enhanced neuronal regeneration when administered after injury. To investigate the spatial mechanisms underlying its neuroregenerative therapeutic effects, we examined brain proteomic responses to post-ischemic NRG-1 treatment in mice using NanoString Digital Spatial Profiling (DSP). Adult C57BL/6 mice were subjected to photothrombotic middle cerebral artery occlusion (MCAO) and treated with NRG-1β (5 μg/kg/day) or vehicle at 24- and 48-h post-stroke. Brains were collected at 3 days post-ischemia for spatial proteomic analysis of 68 neural proteins across the ischemic core, peri-infarct tissue, and peri-infarct normal tissue (PiNT). While NRG-1 did not significantly alter overall neuronal death, it markedly reshaped the neuroregenerative milieu, upregulating myelin basic protein (MBP) and synaptophysin and attenuating inflammatory mediators (SPP1, P2RX7, and CD39). NRG-1 also enhanced expression of autophagy and mitophagy markers (ULK1, LC3B, ATG5, PINK1, and Park7), suggesting restoration of cellular clearance and mitochondrial quality control. Pathway and network analyses revealed activation of neuroregeneration, autophagy, and lysosomal biogenesis pathways, while suppressing neuroinflammatory signaling. These findings demonstrate that delayed NRG-1 therapy, even when initiated 24 h after stroke, induces early molecular programs that prime an anti-inflammatory and neuroregenerative environment. The results support further development of NRG-1 as a clinically translatable, multimodal therapy for extending the post-stroke treatment window and promoting functional recovery. - Source: PubMed
Publication date: 2026/06/02
Noll Jessica MMcGinley ChristopherAugello Catherine JKürüm EsraPan LiuliuPavenko AnnaNam AndyFord Byron DFord Gregory D - Schistosomiasis-associated pulmonary hypertension (Sch-PH) is the most common form of group I PH worldwide. Recently, data revealed that the preclinical Sch-PH animal model exhibited gut and lung microbiome dysbiosis, associated with significant lung endothelial cell (EC) dysfunction and microvascular apoptosis. However, the role of pro-/antiapoptosis sensors, such as the inhibitor of apoptosis protein 2 (c-IAP2) and the purinergic receptor P2X7 (P2X7R), remained unclear. Using Cdh5cre-ER;cIAP1;cIAP2 animal model, this study investigated the contribution of endothelial c-IAP2 in this process, revealing pulmonary P2X7R overexpression as a putative target in the onset of Sch-PH. Pharmacologically, inhibition of P2X7R function confirmed its role in promoting lung EC death and disease progression. Moreover, data suggest that microbiome-associated metabolic alterations in Sch-PH seem linked to microvascular EC apoptosis driven by ATP/P2X7R overactivation and suppressed c-IAP2 expression. Indeed, genetic ablation of endothelial c-IAP2 expression was sufficient to induce PH-like features in mice, with echocardiography indicating a higher pulmonary acceleration time (PAT), PAT/pulmonary ejection time, and right ventricular free wall thickness (RVFWTH) after IP/IV-Egg challenge compared to controls, an effect linked to the female prevalence of the disease. These findings suggest a significant contribution of lung EC-P2X7R activation and c-IAP2 suppression to sex-linked Sch-PH pathology, highlighting them as promising therapeutic targets for this life-threatening illness. - Source: PubMed
Publication date: 2026/06/15
Villarreal Elizabeth SueMarinho YgorLoya OmarAboagye Samuel YawCosta GabrielaOliveira FernandaGupta MuskanOliveira Katia CostaSilva Claudia Lucia MartinsSun JunErzurum Serpil CemLutz Sarah ElizabethWilliams David LeeOliveira Rudolf Feitoza Krawczenkode Jesus Perez VinicioOliveira Suellen Darc - P2X receptors (P2XRs) are ATP-gated cation channels that play a pivotal role in chronic visceral pain (CVP). This review highlights the central contribution of the ATP-P2X3/4/7 axis in peripheral and central sensitization underlying CVP. Recent discoveries have identified the non-coding RNA miR-1306-3p as an endogenous nanomolar agonist of P2X3 receptors, coupling chronic stress to visceral pain via an epigenetic pathway. Moreover, persistent DNA methylation changes at the P2RX7 locus in spinal astrocytes create a "pain memory" that limits the durability of conventional antagonists. The first-generation P2X3/P2X7 antagonists (e.g., AF-219, AZD-9056, NC-2600) failed in clinical trials, primarily due to species-specific receptor pharmacology, the lack of ATP-based biomarkers for patient stratification, and irreversible central sensitization driven by epigenetic marks. To overcome these hurdles, we propose a precision-medicine framework that includes: (1) CRISPR-dCas9-based epigenome editing as a potential one-time "pain-memory eraser"; (2) patient stratification using sweat-ATP levels; and (3) human iPSC-derived neuron screening to improve translational predictability. This integrated approach holds promise not only for CVP related to irritable bowel syndrome (IBS), but also for other pain conditions. - Source: PubMed
Publication date: 2026/06/04
Shen BiyuZhang Hong-HongWang CailinXu XueZhang YingBai TingChen HaoyangIlles PeterTang YongXu Guang-Yin