Characterization of the Mouse Myeloid-associated Differentiation Marker (Myadm) Gene: Promoter Analysis and Protein Localization

Dannaeus, Karin; Bessonova, Marina; Jönsson, Jan‐Ingvar

doi:10.1007/s11033-005-0753-x

Cited by 7 publications

(10 citation statements)

References 38 publications

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“…MYADM is a multi-pass membrane protein that has 8 membrane spanning regions (Fig. 1 C), whose most well-known function is influencing differentiation of myeloid cells 35 , 36 . Since our primary objective was to identify potential targets for extracellular binding of SP-A to eosinophils and MYADM was the sole membrane-associated protein from Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DNPEP is a cytosolic aminopeptidase, an enzyme that has preference for aspartate residues 40 , and is important for intracellular metabolism 41 . MYADM, the only membrane-associated 35 protein pulled-down, is a multi-pass membrane protein that has 8 membrane spanning regions, whose most well-known function is tied to its upregulation during multipotent progenitor cell differentiation, influencing differentiation into myeloid cells 35 , 36 . Functional experiments revealed that MYADM antibody blockade of this membrane protein significantly diminished the ability of SP-A to induce eosinophil apoptosis in both mouse and human eosinophils in vitro and that inhibition of the SP-A:MYADM interaction resulted in worse asthma phenotypes in two different mouse models.…”

Section: Discussionmentioning

confidence: 99%

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Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity

Langlais

Barker

et al. 2021

Sci Rep

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Surfactant protein A (SP-A) is well-known for its protective role in pulmonary immunity. Previous studies from our group have shown that SP-A mediates eosinophil activities, including degranulation and apoptosis. In order to identify potential binding partners on eosinophils for SP-A, eosinophil lysates were subjected to SP-A pull-down and tandem mass spectrometry (MS/MS) analysis. We identified one membrane-bound protein, myeloid-associated differentiation marker (MYADM), as a candidate SP-A binding partner. Blocking MYADM on mouse and human eosinophils ex vivo prevented SP-A from inducing apoptosis; blocking MYADM in vivo led to increased persistence of eosinophilia and airway hyper-responsiveness in an ovalbumin (OVA) allergy model and increased airways resistance and mucus production in a house dust mite (HDM) asthma model. Examination of a subset of participants in the Severe Asthma Research Program (SARP) cohort revealed a significant association between epithelial expression of MYADM in asthma patients and parameters of airway inflammation, including: peripheral blood eosinophilia, exhaled nitric oxide (FeNO) and the number of exacerbations in the past 12 months. Taken together, our studies provide the first evidence of MYADM as a novel SP-A-associated protein that is necessary for SP-A to induce eosinophil apoptosis and we bring to light the potential importance of this previously unrecognized transmembrane protein in patients with asthma.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity

Langlais

Barker

et al. 2021

Sci Rep

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“…It consists of 3 exons and 2 introns, and it spans a 7.1-Kb genomic region [6]. The MYADM protein is located in the nuclear envelope and cytoplasmic inner membrane, forming a complete membrane protein [7,8]. Previous studies have found that MYADM is selectively expressed in myeloid cells [9], participates in the process of myeloid differentiation [6], and relates to the differentiation of hematopoietic cells.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Bioinformatic Analysis for Identification of Myeloid-Associated Differentiation Marker as a Potential Negative Prognostic Biomarker in Non-Small-Cell Lung Cancer

Zhou¹,

Chen²,

Gu³

et al. 2022

Pathol. Oncol. Res.

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Objectives: This study aimed to identify a molecular marker associated with the prognosis of non-small-cell lung cancer (NSCLC).Materials and Methods: The RNA sequencing data and clinical information of NSCLC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression gene modules and differentially expressed genes (DEGs) by comparing gene expression between NSCLC tumor tissues and normal tissues. Subsequently, the functional enrichment analysis of the DEGs was performed. Kaplan-Meier survival analysis and the GEPIA2 online tool were performed to investigate the relationship between the expression of these genes of interest and the survival of NSCLC patients, and to validate one most survival-relevent hub gene, as well as validated the hub gene using independent datasets from the GEO database. Further analysis was carried out to characterize the relationship between the hub gene and tumor immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and other known biomarkers of lung cancer. The related genes were screened by analyzing the protein-protein interaction (PPI) network and the survival model was constructed. GEPIA2 was applied in the potential analysis of pan-cancer biomarker of hub gene.Results: 57 hub genes were found to be involved in intercellular connectivity from the 779 identified differentially co-expressed genes. Myeloid-associated differentiation marker (MYADM) was strongly associated with overall survival (OS) and disease-free survival (DFS) of NSCLC patients, and high MYADM expression was associated with poor prognosis. Thus, MYADM was identified as a risk factor. Additionally, MYADM was validated as a survival risk factor in NSCLC patients in two independent datasets. Further analysis showed that MYADM was nagetively associated with TMB, and was positively correlated with macrophages, neutrophils, and dendritic cells, suggesting its role in regulating tumor immunity. The MYADM expression differed across many types of cancer and had the potential to serve as a pan-cancer marker.Conclusion:MYADM is an independent prognostic factor for NSCLC patients, which can predict the progression of cancer and play a role in the tumor immune cell infiltration in NSCLC.

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“…The region carrying the MYADM -like gene family has been reported to be conserved throughout many mammalian species (i.e., cow, pig, goat) 35 , 36 . Protein products synthesized by the MYADM gene family have been reported to be involved in membrane formation and regulatory processes in myeloid cell lines 37 , 38 . In addition to these functions, the increase of MYADM gene expression levels in pluripotent cells is involved in the completion of erythropoiesis 38 .…”

Section: Discussionmentioning

confidence: 99%

Estimates of genomic heritability and genome-wide association studies for blood parameters in Akkaraman sheep

Arzık

Kızılaslan

White

et al. 2022

Sci Rep

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The aim of this study was to estimate genomic heritability and the impact that genetic backgrounds have on blood parameters in Akkaraman sheep by conducting genome-wide association studies and regional heritability mapping analysis. Genomic heritability estimates for blood parameters ranged from 0.00 to 0.55, indicating that measured phenotypes have a low to moderate heritability. A total of 7 genome- and 13 chromosome-wide significant SNPs were associated with phenotypic changes in 15 blood parameters tested. Accordingly, SCN7A, SCN9A, MYADM-like, CCDC67, ITGA9, MGAT5, SLC19A1, AMPH, NTRK2, MSRA, SLC35F3, SIRT6, CREB3L3, and NAV3 genes as well as three undefined regions (LOC101117887, LOC106991526 and LOC105608461) were suggested as candidates. Most of the identified genes were involved in basic biological processes that are essential to immune system function and cellular growth; specific functions include cellular transport, histone deacetylation, cell differentiation, erythropoiesis, and endocytosis. The top significant SNP for HCT, MCH, and MCHC was found within a genomic region mainly populated by the MYADM-like gene family. This region was previously suggested to be under historical selection pressure in many sheep breeds from various parts of the world. These results have implications on animal breeding program studies due to the effect that the genetic background has on blood parameters, which underlying many productive and wellness related traits.

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Characterization of the Mouse Myeloid-associated Differentiation Marker (Myadm) Gene: Promoter Analysis and Protein Localization

Cited by 7 publications

References 38 publications

Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity

Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity

A Comprehensive Bioinformatic Analysis for Identification of Myeloid-Associated Differentiation Marker as a Potential Negative Prognostic Biomarker in Non-Small-Cell Lung Cancer

Estimates of genomic heritability and genome-wide association studies for blood parameters in Akkaraman sheep

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