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Sci Rep. 2017 Jun 27;7(1):4290. doi: 10.1038/s41598-017-04561-4.

IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model.

Author information

1
Lung Cancer and Respiratory Diseases Unit, Centro de Investigación Biomédica de La Rioja (CIBIR), Fundación Rioja Salud, Logroño, Spain.
2
Genomics Core Facility, Centro de Investigación Biomédica de La Rioja (CIBIR), Fundación Rioja Salud, Logroño, Spain.
3
Molecular Neurobiology Unit, Centro de Investigación Biomédica de la Rioja (CIBIR), Fundación Rioja Salud, Logroño, Spain.
4
Pneumology Service, Hospital San Pedro, Logroño, Spain.
5
Lung Cancer and Respiratory Diseases Unit, Centro de Investigación Biomédica de La Rioja (CIBIR), Fundación Rioja Salud, Logroño, Spain. jgpichel@riojasalud.es.

Abstract

IGF1R (Insulin-like Growth Factor 1 Receptor) is a tyrosine kinase with pleiotropic cellular functions. IGF activity maintains human lung homeostasis and is implicated in pulmonary diseases such as cancer, ARDS, COPD, asthma and fibrosis. Here we report that lung transcriptome analysis in mice with a postnatally-induced Igf1r gene deletion showed differentially expressed genes with potentially protective roles related to epigenetics, redox and oxidative stress. After bleomycin-induced lung injury, IGF1R-deficient mice demonstrated improved survival within a week. Three days post injury, IGF1R-deficient lungs displayed changes in expression of IGF system-related genes and reduced vascular fragility and permeability. Mutant lungs presented reduced inflamed area, down-regulation of pro-inflammatory markers and up-regulation of resolution indicators. Decreased inflammatory cell presence in BALF was reflected in diminished lung infiltration mainly affecting neutrophils, also corroborated by reduced neutrophil numbers in bone marrow, as well as reduced lymphocyte and alveolar macrophage counts. Additionally, increased SFTPC expression together with hindered HIF1A expression and augmented levels of Gpx8 indicate that IGF1R deficiency protects against alveolar damage. These findings identify IGF1R as an important player in murine acute lung inflammation, suggesting that targeting IGF1R may counteract the inflammatory component of many lung diseases.

PMID:
28655914
PMCID:
PMC5487362
DOI:
10.1038/s41598-017-04561-4
[Indexed for MEDLINE]
Free PMC Article

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