Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells
| Autor: | Dhruma Thakker, Robert J. Hall, Ian P. Hall, Charlotte K. Billington, Jonathan O’Loughlin, Ian Sayers |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Respiratory System Mutation Missense Single-nucleotide polymorphism Genome-wide association study Bronchi Biology Biochemistry Receptors G-Protein-Coupled 03 medical and health sciences Pulmonary Disease Chronic Obstructive 0302 clinical medicine Genetics Humans Receptor Molecular Biology Gene Cells Cultured Cell Proliferation Cell growth Epithelial Cells Muscle Smooth Genomics Cell biology CTGF 030104 developmental biology Expression quantitative trait loci Functional genomics 030217 neurology & neurosurgery Biotechnology Signal Transduction |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 35(7) |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | GPR126 is an adhesion G protein-coupled receptor which lies on chromosome 6q24. Genetic variants in this region are reproducibly associated with lung function and COPD in genome wide association studies (GWAS). The aims of this study were to define the role of GPR126 in the human lung and in pulmonary disease and identify possible casual variants. Online tools (GTEx and LDlink) identified SNPs which may have effects on GPR126 function/ expression, including missense variant Ser123Gly and an intronic variant that shows eQTL effects on GPR126 expression. GPR126 signaling via cAMP-mediated pathways was identified in human structural airway cells when activated with the tethered agonist, stachel. RNA-seq was used to identify downstream genes/ pathways affected by stachel-mediated GPR126 activation in human airway smooth muscle cells. We identified ~350 differentially expressed genes at 4 and 24 hours post stimulation with ~20% overlap. We identified that genes regulated by GPR126 activation include IL33, CTGF, and SERPINE1, which already have known roles in lung biology. Pathways altered by GPR126 included those involved in cell cycle progression and cell proliferation. Here, we suggest a role for GPR126 in airway remodeling. |
| Databáze: | OpenAIRE |
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