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      Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?

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          Abstract

          Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.

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          Most cited references81

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          Proteomics. Tissue-based map of the human proteome.

          Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
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            Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.

            R. Edgar (2002)
            The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data. GEO provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-throughput gene expression and genomic hybridization experiments. GEO is not intended to replace in house gene expression databases that benefit from coherent data sets, and which are constructed to facilitate a particular analytic method, but rather complement these by acting as a tertiary, central data distribution hub. The three central data entities of GEO are platforms, samples and series, and were designed with gene expression and genomic hybridization experiments in mind. A platform is, essentially, a list of probes that define what set of molecules may be detected. A sample describes the set of molecules that are being probed and references a single platform used to generate its molecular abundance data. A series organizes samples into the meaningful data sets which make up an experiment. The GEO repository is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo.
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              The Genotype-Tissue Expression (GTEx) project.

              Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
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                Author and article information

                Contributors
                Journal
                Front Allergy
                Front Allergy
                Front. Allergy
                Frontiers in Allergy
                Frontiers Media S.A.
                2673-6101
                2673-6101
                31 May 2021
                2021
                : 2
                : 677677
                Affiliations
                [1] 1Division of Respiratory Medicine, Nottingham Biomedical Research Centre, National Institute for Health Research, University of Nottingham Biodiscovery Institute, University of Nottingham , Nottingham, United Kingdom
                [2] 2Orion Corporation, Orion Pharma, Research and Development , Turku, Finland
                Author notes

                Edited by: Christopher D. Pascoe, University of Manitoba, Canada

                Reviewed by: Tobias Müller, University Hospital RWTH Aachen, Germany; Murali Prakriya, Northwestern University, United States

                *Correspondence: Ian P. Hall ian.hall@ 123456nottingham.ac.uk

                This article was submitted to Asthma, a section of the journal Frontiers in Allergy

                Article
                10.3389/falgy.2021.677677
                8974712
                35386996
                3871b332-279b-45e3-86ba-9e87729c6573
                Copyright © 2021 Thompson, Sayers, Kuokkanen and Hall.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 March 2021
                : 30 April 2021
                Page count
                Figures: 5, Tables: 4, Equations: 0, References: 81, Pages: 16, Words: 11457
                Categories
                Allergy
                Review

                purinergic signaling,purinergic receptor,lung,airway,bioinformatics,gene expression,asthma

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