Ask about this productRelated genes to: ENPP2 antibody
- Gene:
- ENPP2 NIH gene
- Name:
- ectonucleotide pyrophosphatase/phosphodiesterase 2
- Previous symbol:
- PDNP2
- Synonyms:
- ATX, PD-IALPHA
- Chromosome:
- 8q24.12
- Locus Type:
- gene with protein product
- Date approved:
- 1995-08-10
- Date modifiied:
- 2015-09-11
Related products to: ENPP2 antibody
Related articles to: ENPP2 antibody
- Hepatic encephalopathy (HE) is a debilitating neuropsychiatric condition associated with acute liver failure or advanced liver diseases, significantly affecting patient morbidity and mortality. Autotaxin (ATX), a lysophospholipase D that generates lysophosphatidic acid (LPA), has been proposed as a biomarker for liver fibrosis progression, but its role in HE remains poorly defined. This study aimed to explore the potential roles of ATX using in vivo TAA-induced HE models in mouse and clinical evaluations of cirrhotic patients with and without HE. ATX concentrations were quantified in plasma, liver tissue, and frontal cortex of HE mice, while ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) gene expression and LPA levels were assessed in murine salivary glands. In parallel, serum and salivary ATX were measured in 7 cirrhotic patients with HE and 12 cirrhotic patients without HE. ATX concentrations were significantly elevated in the liver parenchyma and frontal cortex of TAA-induced HE mice compared to controls, whereas plasma ATX showed no significant difference. Enpp2 expression was upregulated 2.49-fold in salivary glands of HE mice, although salivary LPA concentrations did not differ between groups. Clinically, both serum and salivary ATX levels were significantly higher in cirrhotic patients with HE than in those without HE. Moreover, salivary ATX levels positively correlated with serum alkaline phosphatase (ALP) levels in the HE patient group. These findings demonstrate that ATX is elevated in key tissues and biofluids in both experimental and clinical HE, supporting its potential as a novel biomarker. Moreover, the data suggest that the ATX-LPA axis may contribute to HE pathophysiology, providing a foundation for future mechanistic studies and the exploration of targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/05/31
Sepehrinezhad AliZarei HosseinMehravaran FarhadSadr SepehrAhmad Meysam HeydarRezaeitalab FariborzMahyad MahshidHajali VahidShahbazi AliBeheshti Namdar AliSahab Negah Sajad - In this study, new imidazo[1,2-a]pyrazine derivative 15 (YS3074) and pyrazine derivative 17 (YS3375) are identified and optimized as potent and selective ENPP1 inhibitors. Compounds 15 and 17 both exhibited high potency and selectivity toward ENPP1 (IC = 4.23 nM and 19.4 nM, respectively) with negligible ENPP2 inhibition (>10 μM) and weak ENPP3 inhibition (>3 μM). Both enhanced cGAMP-induced expression of STING pathway genes (IFNB1, CXCL10, IL6) in a concentration-dependent manner without cytotoxicity, producing stronger and more sustained activation than MV-658. This effect, dependent on the cGAMP-STING axis, was attributed to inhibition of ENPP1-mediated cGAMP hydrolysis. Additionally, compounds 15 and 17 showed no inhibition of the hERG channel (IC > 30 μM), indicating a favorable cardiac safety profile. In the CT-26 colorectal cancer model, compounds 15 and 17, administered at 40 mg/kg in combination with an anti-PD-1 antibody, achieved superior tumor growth inhibition (TGI: 73% and 67%, respectively), significantly prolonged survival, and were well tolerated with no observable body weight loss. These results establish 15 and 17 as promising ENPP1 inhibitors with favorable safety profiles, supporting their potential in combination cancer immunotherapy. - Source: PubMed
Publication date: 2026/08/25
He ZhiyueZhang YingyingZhan ShipingCao TianBai WanruZhou BozhiYu JieZeng HuiyingZhou JingyiTian FuyunChen XiaoyanZhang SulinZheng MingyueWu Xiaowei - With recent advances in high-throughput proteomic technologies, population-scale plasma proteomics datasets, often linked to extensive genetic and phenotypic information, have become increasingly accessible. Yet the relationships between circulating protein levels, brain imaging phenotypes, and risk for neurological and psychiatric disorders remain largely unexplored. Proteome-wide association studies offer a promising approach for elucidating biological mechanisms that connect genetic variation to complex brain-related traits and diseases. In this study, we integrated protein quantitative trait loci (pQTLs) from the two largest plasma proteomic resources (the UK Biobank Pharma Proteomics Project [UKB-PPP] and Ferkingstad [deCODE]) with genome-wide association studies of brain imaging-derived phenotypes in UK Biobank using Mendelian randomization and colocalization analyses. We identified 120 cis and 20 trans associations between plasma proteins and imaging phenotypes and validated these findings using brain tissue-derived proteomic and transcriptomic datasets. Multivariable Mendelian randomization revealed eleven plasma proteins (coding genes and ) with significant direct effects on the risk of Alzheimer's disease, Parkinson's disease, multiple sclerosis, bipolar disorder, and schizophrenia. Single-cell expression and pathway enrichment analyses further revealed cell-type-specific effects and distinct biological processes underlying these protein-disease associations. Together, these findings demonstrate robust links between plasma protein variation and brain structure, delineate protein-disease pathways, and highlight the cellular and molecular mechanisms that contribute to neurobiological diversity and pathology. - Source: PubMed
Publication date: 2026/07/15
Ayubcha CyrusDennis EvanBhattacharyya UpasanaJohn JibinLam MaxLencz ToddGe TianChen Chia-Yen - To systematically characterize aqueous humor (AH) proteomic alterations in ADAMTSL4-associated congenital ectopia lentis (CEL) and to identify disease-related molecular features. - Source: PubMed
Chen XinyaoShen XinJia WannanWang YaleiHuo QiuyiXiao YanboZhang YulinLi LinzhaoGao XuqingA GuangqiYang FengjingChen YilinChen TianhuiZhang MinYang JinPi YanChen ZexuJiang Yongxiang - Chronic exposure to ultraviolet B (UVB) radiation induces excessive reactive oxygen species (ROS) production in dermal fibroblasts, leading to cellular senescence and skin photoaging. Ageing skin is characterised by disruption of the immune microenvironment, including impaired macrophage polarisation and reduced M2 macrophage activity. However, the contribution of M2 macrophages to fibroblast photoaging remains incompletely understood. Here, we investigated whether M2 macrophages attenuate UVB-induced fibroblast senescence through ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2)-dependent lysophosphatidic acid (LPA)signalling. UVB-induced L929 fibroblasts were treated with conditioned media derived from polarised RAW264.7 macrophages, with or without ENPP2 silencing. UVB exposure induced marked senescence, oxidative stress, and mitophagy impairment, whereas conditioned medium from M2 macrophages significantly alleviated these effects compared with M1-derived conditioned medium. Notably, ENPP2 depletion in M2 macrophages substantially reduced these protective effects. M2 macrophage-derived conditioned medium contained elevated LPA levels and restored UVB-suppressed LPAR1 and LPAR3 expression in fibroblasts. Pharmacological inhibition of LPAR1/3 attenuated the protective effects of M2 macrophages, while exogenous LPA supplementation restored these effects under ENPP2-deficient conditions. These changes were associated with enhanced PINK1/Parkin-related mitophagy signalling and reduced oxidative stress. Collectively, these findings identify M2 macrophage-derived ENPP2/LPA signalling as a critical paracrine mechanism that mitigates UVB-induced fibroblast photoaging. - Source: PubMed
Lu MeiqiWang XiaoyangHu YujieJia ShanshanQi YongjunJiao YaZhao JieWang XiaochuanZhang JixunJiang Duyin