ENPP3

The Long Life Family Study (LLFS) enrolled 4,953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2...

BACKGROUND: The mechanism of Nicotinamide Adenine Dinucleotide (NAD+) metabolism-related genes (NMRGs) in diabetic peripheral neuropathy (DPN) is unclear. This study aimed to find new NMRGs biomarkers in DPN. METHODS: DPN related datasets GSE95849 and GSE185011 were acquired from the Gene Expression Omnibus (GEO) database. 51 NMRGs were collected from a previous article. To explore NMRGs expression in DPN and control samples, differential expression analysis was completed in GSE95849 to obtain differentially expressed genes (DEGs), and the intersection of DEGs and NMRGs was regarded as DE-NMRGs...

PURPOSE: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis. METHODS: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC)...

cGAMP is a second messenger that is synthesized in the cytosol upon detection of cytosolic dsDNA and passed between cells to facilitate downstream immune signaling. ENPP1, an extracellular enzyme, was the only metazoan cGAMP hydrolase known to regulate cGAMP levels to dampen anti-cancer immunity. Here, we uncover ENPP3 as the second and only other metazoan cGAMP hydrolase under homeostatic conditions. ENPP3 has a tissue expression pattern distinct from that of ENPP1 and accounts for all remaining cGAMP hydrolysis activity in mice lacking ENPP1...

Growing evidence indicates that aberrant methylation is pivotal in the development and progression of endometriosis (EMs). This study explores the relationship between abnormal methylation of the ENPP3 promoter and the pathogenesis of ovarian EMs, focusing on its regulatory effect on ENPP3 expression. We analyzed the methylation levels of ENPP3 in ectopic endometrial tissues from ovarian EMs patients and in normal endometrial tissues from women without EMs. The expression and distribution of ENPP3 were evaluated using RT-qPCR and immunohistochemistry...

Purinergic signaling is important for normal bladder function, as it is thought to initiate the voiding reflex and modulate smooth muscle tone. The availability of adenine nucleotides and nucleosides (aka purines) at receptor sites of various cell types in the bladder wall is regulated by ectonucleotidases (ENTDs). ENTDs hydrolyze purines such as adenosine 5'-triphosphate (ATP) and adenosine 5'-diphosphate (ADP) with varying preference for the individual substrate. Therefore, the end effect of extracellular purines may depend significantly on the type of ENTD that is expressed in close proximity to the target cells...

OBJECTIVE: Spinal cord injury (SCI) can disrupt membrane transmission by affecting transmembrane channels or neurotransmitter release. This study aimed to explore gene expression changes of transmembrane proteins underlying SCI through bioinformatics approaches and confirming in SCI model in rats. MATERIALS AND METHODS: In this experimental study, the differentially expressed genes (DEGs) in acute and subacute SCI were obtained based on microarray data downloaded from the gene expression omnibus (GEO)...

Ectonucleotidases inhibitors (ENPPs, e5'NT (CD73) and h -TNAP) are potential therapeutic candidates for the treatment of cancer. Adenosine, the cancer-developing, and growth moiety is the resultant product of these enzymes. The synthesis of small molecules that can increase the acidic and ionizable structure of adenosine 5-monophosphate (AMP) has been used in traditional attempts to inhibit ENPPs, ecto-5'-nucleotidase and h -TNAP. In this article, we present a short and interesting method for developing substituted indole acetic acid sulfonate derivatives (5a-5o), which are non-nucleotide based small molecules, and investigated their inhibitory potential against recombinant h -ENPP1, h -ENPP3, h -TNAP, h -e5'NT and r -e5'NT...

BACKGROUND: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. METHODS: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded...

For decades, studies of snake venoms focused on the venom-ome-specific toxins (VSTs). VSTs are dominant soluble proteins believed to contribute to the main venomous effects and emerged into gene clusters for fast adaptation and diversification of snake venoms. However, the conserved minor venom components, such as snake venom phosphodiesterase (svPDE), remain largely unexplored. Here, we focus on svPDE by genomic and transcriptomic analysis across snake clades and demonstrate that soluble svPDE is co-opted from the ancestral membrane-attached ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3) gene by replacing the original 5' exon with the exon encoding a signal peptide...

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal and irreversible interstitial lung disease. The specific mechanisms involved in the pathogenesis of IPF are not fully understood, while metabolic dysregulation has recently been demonstrated to contribute to IPF. This study aims to identify key metabolism-related genes involved in the progression of IPF, providing new insights into the pathogenesis of IPF. Methods: We downloaded four datasets (GSE32537, GSE110147, GSE150910, and GSE92592) from the Gene Expression Omnibus (GEO) database and identified differentially expressed metabolism-related genes (DEMRGs) in lung tissues of IPF by comprehensive analysis...

The β-lactoglobulin (β-LG) was previously characterized as a mild antioxidant modulating cell viability. However, its biological action regarding endometrial stromal cell cytophysiology and function has never been considered. In this study, we investigated the influence of β-LG on the cellular status of equine endometrial progenitor cells under oxidative stress. The study showed that β-LG decreased the intracellular accumulation of reactive oxygen species, simultaneously ameliorating cell viability and exerting an anti-apoptotic effect...

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies...

Adenosine 5′-triphosphate (ATP) is released in the bladder lumen during filling. Urothelial ATP is presumed to regulate bladder excitability. Urinary ATP is suggested as a urinary biomarker of bladder dysfunctions since ATP is increased in the urine of patients with overactive bladder, interstitial cystitis or bladder pain syndrome. Altered urinary ATP might also be associated with voiding dysfunctions linked to disease states associated with metabolic syndrome. Extracellular ATP levels are determined by ATP release and ATP hydrolysis by membrane-bound and soluble nucleotidases (s-NTDs)...

Aberrant level of ectonucleotide pyrophosphatase/phosphodiesterase-1 and -3 is linked with numerous disorders, for instance, diabetes, cancer, osteoarthritis, chondrocalcinosis, and allergic reactions. These disorders may be cured or minimized by blocking the activity of ENPP1 and ENPP3 isozymes. In this study, arylamide sulphonates were synthesized, characterized, and evaluated for their capability to affect the activity of isozymes ENPP1 and ENPP3. Among the selective inhibitors of ENPP1, compounds 4f and 4q exhibited sub-micromolar IC50 values of 0...

Prior studies suggest that urothelium-released adenosine 5'-triphosphate (ATP) has a prominent role in bladder mechanotransduction. Urothelial ATP regulates the micturition cycle through activation of purinergic receptors that are expressed in many cell types in the lamina propria (LP), including afferent neurons, and might also be important for direct mechanosensitive signaling between urothelium and detrusor. The excitatory action of ATP is terminated by enzymatic hydrolysis, which subsequently produces bioactive metabolites...

Ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family members (ENPP1-7) have been implicated in key biological and pathophysiological processes, including nucleotide and phospholipid signaling, bone mineralization, fibrotic diseases, and tumor-associated immune cell infiltration. ENPPs are single-pass transmembrane ecto-enzymes, with notable exceptions of ENPP2 (Autotaxin) and ENNP6, which are secreted and glycosylphosphatidylinositol (GPI)-anchored, respectively. ENNP1 and ENNP2 are the best characterized and functionally the most interesting members...

Restenosis is the main restriction on the long-term efficacy of percutaneous transluminal angioplasty (PTA) therapy for peripheral artery disease (PAD). Interventions to prevent restenosis are poor, and the exact mechanism is unclear. Here, we aimed to elucidate the role of GRIA2 in the restenosis process post-PTA in lower extremity arteries. We searched the differentially expressed genes (DEGs) between atherosclerotic and restenotic artery plaques in the Gene Expression Omnibus (GEO), and five DEGs were identified...

Introduction: Synovial sarcoma (SS) is one of the most invasive soft tissue sarcomas, prone to recurrence and metastasis, and the efficacy of surgical treatment and chemotherapy for SS remains poor. Therefore, the diagnosis and treatment of SS remain a significant challenge. This study aimed to analyze the mutated genes of primary SS (PSS) and recurrent SS (RSS), discover whether these sarcomas exhibit some potential mutated genes, and then predict associated microRNAs (miRNA) and circular RNAs (circRNA) by analyzing the mutated genes...

LESSONS LEARNED: The primary endpoint of this phase II study that evaluated the efficacy and safety of the investigational compound, AGS-16C3F, versus axitinib in previously treated patients with metastatic renal cell carcinoma (mRCC) was not met. Median progression-free survival, the primary endpoint, was 2.9 months with AGS-16C3F and 5.7 months with axitinib (HR, 1.676; 95% CI, 1.107-2.537; p = .015), per investigator assessment The safety profile for each study drug was as expected, with the most commonly reported adverse events being fatigue (53%) and nausea (47%) in the AGS-16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm...