Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine

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Koli , K , Sutinen , E , Ronty , M , Rantakari , P , Fortino , V , Pulkkinen , V , Greco , D , Sipila , P & Myllarniemi , M 2016 , ' Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine ' , PLoS One , vol. 11 , no. 7 , 0159010 . https://doi.org/10.1371/journal.pone.0159010

Title: Gremlin-1 Overexpression in Mouse Lung Reduces Silica-Induced Lymphocyte Recruitment - A Link to Idiopathic Pulmonary Fibrosis through Negative Correlation with CXCL10 Chemokine
Author: Koli, Katri; Sutinen, Eva; Ronty, Mikko; Rantakari, Pia; Fortino, Vittorio; Pulkkinen, Ville; Greco, Dario; Sipila, Petra; Myllarniemi, Marjukka
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Clinicum
University of Helsinki, Department of Pathology
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2016-07-18
Language: eng
Number of pages: 20
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/167008
Abstract: 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.
Subject: BONE MORPHOGENETIC PROTEIN
MIGRATION INHIBITORY FACTOR
TO-MESENCHYMAL TRANSITION
GENE-EXPRESSION PATTERNS
TRANSGENIC MICE
IN-VIVO
ANTAGONIST
GROWTH
RECOMBINATION
INFLAMMATION
3111 Biomedicine
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