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

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 m...

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Autores principales:	Sergio Piñeiro-Hermida, Icíar P. López, Elvira Alfaro-Arnedo, Raquel Torrens, María Iñiguez, Lydia Alvarez-Erviti, Carlos Ruíz-Martínez, José G. Pichel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b2793cee94e4995ba43123296da8895
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spelling	oai:doaj.org-article:3b2793cee94e4995ba43123296da88952021-12-02T12:30:16ZIGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model10.1038/s41598-017-04561-42045-2322https://doaj.org/article/3b2793cee94e4995ba43123296da88952017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04561-4https://doaj.org/toc/2045-2322Abstract 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.Sergio Piñeiro-HermidaIcíar P. LópezElvira Alfaro-ArnedoRaquel TorrensMaría IñiguezLydia Alvarez-ErvitiCarlos Ruíz-MartínezJosé G. PichelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sergio Piñeiro-Hermida Icíar P. López Elvira Alfaro-Arnedo Raquel Torrens María Iñiguez Lydia Alvarez-Erviti Carlos Ruíz-Martínez José G. Pichel IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
description	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.
format	article
author	Sergio Piñeiro-Hermida Icíar P. López Elvira Alfaro-Arnedo Raquel Torrens María Iñiguez Lydia Alvarez-Erviti Carlos Ruíz-Martínez José G. Pichel
author_facet	Sergio Piñeiro-Hermida Icíar P. López Elvira Alfaro-Arnedo Raquel Torrens María Iñiguez Lydia Alvarez-Erviti Carlos Ruíz-Martínez José G. Pichel
author_sort	Sergio Piñeiro-Hermida
title	IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
title_short	IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
title_full	IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
title_fullStr	IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
title_full_unstemmed	IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
title_sort	igf1r deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b2793cee94e4995ba43123296da8895
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IGF1R deficiency attenuates acute inflammatory response in a bleomycin-induced lung injury mouse model

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