Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine
| Autor: | Petra Sipilä, Marjukka Myllärniemi, Pia Rantakari, Katri Koli, Dario Greco, Eva Sutinen, Mikko Rönty, Ville Pulkkinen, Vittorio Fortino |
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| Přispěvatelé: | Research Programs Unit, Translational Cancer Biology (TCB) Research Programme, Katri Koli / Principal Investigator, Transplantation Laboratory, Medicum, Clinicum, Keuhkosairauksien yksikkö, Department of Medicine, Department of Pathology, Ville Pulkkinen Research group |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine Pathology Lung Development Pulmonary Fibrosis Agricultural Biotechnology Organogenesis TO-MESENCHYMAL TRANSITION RECOMBINATION lcsh:Medicine Gene Expression Pathology and Laboratory Medicine Idiopathic pulmonary fibrosis White Blood Cells Mice Fibrosis Animal Cells Pulmonary fibrosis Medicine and Health Sciences Lymphocytes lcsh:Science Immune Response Lung IN-VIVO BONE MORPHOGENETIC PROTEIN TRANSGENIC MICE Multidisciplinary medicine.diagnostic_test biology Genetically Modified Organisms Agriculture Animal Models respiratory system Silicon Dioxide 3. Good health Up-Regulation medicine.anatomical_structure GROWTH Intercellular Signaling Peptides and Proteins Cellular Types Genetic Engineering Research Article Biotechnology medicine.medical_specialty GENE-EXPRESSION PATTERNS Immune Cells Immunology Mouse Models Mice Transgenic Research and Analysis Methods Cell Line 03 medical and health sciences Model Organisms Signs and Symptoms Diagnostic Medicine medicine Genetics CXCL10 Animals Humans ANTAGONIST Inflammation Blood Cells 030102 biochemistry & molecular biology Genetically Modified Animals lcsh:R Biology and Life Sciences Surfactant protein C Cell Biology ta3121 medicine.disease MIGRATION INHIBITORY FACTOR Idiopathic Pulmonary Fibrosis respiratory tract diseases Chemokine CXCL10 030104 developmental biology Bronchoalveolar lavage Cancer research biology.protein lcsh:Q 3111 Biomedicine Interferons Organism Development Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 7, p e0159010 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is characterized by activation and injury of epithelial cells, the accumulation of connective tissue and changes in the inflammatory microenvironment. The bone morphogenetic protein (BMP) inhibitor protein gremlin-1 is associated with the progression of fibrosis both in human and mouse lung. We generated a transgenic mouse model expressing gremlin-1 in type II lung epithelial cells using the surfactant protein C (SPC) promoter and the Cre-LoxP system. Gremlin-1 protein expression was detected specifically in the lung after birth and did not result in any signs of respiratory insufficiency. Exposure to silicon dioxide resulted in reduced amounts of lymphocyte aggregates in transgenic lungs while no alteration in the fibrotic response was observed. Microarray gene expression profiling and analyses of bronchoalveolar lavage fluid cytokines indicated a reduced lymphocytic response and a downregulation of interferon-induced gene program. Consistent with reduced Th1 response, there was a downregulation of the mRNA and protein expression of the anti-fibrotic chemokine CXCL10, which has been linked to IPF. In human IPF patient samples we also established a strong negative correlation in the mRNA expression levels of gremlin-1 and CXCL10. Our results suggest that in addition to regulation of epithelial-mesenchymal crosstalk during tissue injury, gremlin-1 modulates inflammatory cell recruitment and anti-fibrotic chemokine production in the lung. |
| Databáze: | OpenAIRE |
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