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Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis

Background: Fibroblastic foci (FF) are characteristic features of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) and one cardinal feature thought to represent a key mechanism of pathogenesis. Hence, FF have a high impact on UIP/IPF diagnosis in current guidelines. However, al...

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Autores principales: Kamp, Jan C., Neubert, Lavinia, Stark, Helge, Hinrichs, Jan B., Boekhoff, Caja, Seidel, Allison D., Ius, Fabio, Haverich, Axel, Gottlieb, Jens, Welte, Tobias, Braubach, Peter, Laenger, Florian, Hoeper, Marius M., Kuehnel, Mark P., Jonigk, Danny D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870272/
https://www.ncbi.nlm.nih.gov/pubmed/35203313
http://dx.doi.org/10.3390/cells11040664
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author Kamp, Jan C.
Neubert, Lavinia
Stark, Helge
Hinrichs, Jan B.
Boekhoff, Caja
Seidel, Allison D.
Ius, Fabio
Haverich, Axel
Gottlieb, Jens
Welte, Tobias
Braubach, Peter
Laenger, Florian
Hoeper, Marius M.
Kuehnel, Mark P.
Jonigk, Danny D.
author_facet Kamp, Jan C.
Neubert, Lavinia
Stark, Helge
Hinrichs, Jan B.
Boekhoff, Caja
Seidel, Allison D.
Ius, Fabio
Haverich, Axel
Gottlieb, Jens
Welte, Tobias
Braubach, Peter
Laenger, Florian
Hoeper, Marius M.
Kuehnel, Mark P.
Jonigk, Danny D.
author_sort Kamp, Jan C.
collection PubMed
description Background: Fibroblastic foci (FF) are characteristic features of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) and one cardinal feature thought to represent a key mechanism of pathogenesis. Hence, FF have a high impact on UIP/IPF diagnosis in current guidelines. However, although less frequent, these histomorphological hallmarks also occur in other fibrotic pulmonary diseases. Currently, there is therefore a gap in knowledge regarding the underlying molecular similarities and differences of FF in different disease entities. Methods: In this work, we analyzed the compartment-specific gene expression profiles of FF in IPF and sarcoidosis in order to elucidate similarities and differences as well as shared pathomechanisms. For this purpose, we used laser capture microdissection, mRNA and protein expression analysis. Biological pathway analysis was performed using two different gene expression databases. As control samples, we used healthy lung tissue that was donated but not used for lung transplantation. Results: Based on Holm Bonferroni corrected expression data, mRNA expression analysis revealed a significantly altered expression signature for 136 out of 760 genes compared to healthy controls while half of these showed a similar regulation in both groups. Immunostaining of selected markers from each group corroborated these results. However, when comparing all differentially expressed genes with the fdr-based expression data, only 2 of these genes were differentially expressed between sarcoidosis and IPF compared to controls, i.e., calcium transport protein 1 (CAT1) and SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), both in the sarcoidosis group. Direct comparison of sarcoidosis and IPF did not show any differentially regulated genes independent from the statistical methodology. Biological pathway analysis revealed a number of fibrosis-related pathways pronounced in IPF without differences in the regulatory direction. Conclusions: These results demonstrate that FF of end-stage IPF and sarcoidosis lungs, although different in initiation, are similar in gene and protein expression, encouraging further studies on the use of antifibrotic agents in sarcoidosis.
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spelling pubmed-88702722022-02-25 Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis Kamp, Jan C. Neubert, Lavinia Stark, Helge Hinrichs, Jan B. Boekhoff, Caja Seidel, Allison D. Ius, Fabio Haverich, Axel Gottlieb, Jens Welte, Tobias Braubach, Peter Laenger, Florian Hoeper, Marius M. Kuehnel, Mark P. Jonigk, Danny D. Cells Article Background: Fibroblastic foci (FF) are characteristic features of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) and one cardinal feature thought to represent a key mechanism of pathogenesis. Hence, FF have a high impact on UIP/IPF diagnosis in current guidelines. However, although less frequent, these histomorphological hallmarks also occur in other fibrotic pulmonary diseases. Currently, there is therefore a gap in knowledge regarding the underlying molecular similarities and differences of FF in different disease entities. Methods: In this work, we analyzed the compartment-specific gene expression profiles of FF in IPF and sarcoidosis in order to elucidate similarities and differences as well as shared pathomechanisms. For this purpose, we used laser capture microdissection, mRNA and protein expression analysis. Biological pathway analysis was performed using two different gene expression databases. As control samples, we used healthy lung tissue that was donated but not used for lung transplantation. Results: Based on Holm Bonferroni corrected expression data, mRNA expression analysis revealed a significantly altered expression signature for 136 out of 760 genes compared to healthy controls while half of these showed a similar regulation in both groups. Immunostaining of selected markers from each group corroborated these results. However, when comparing all differentially expressed genes with the fdr-based expression data, only 2 of these genes were differentially expressed between sarcoidosis and IPF compared to controls, i.e., calcium transport protein 1 (CAT1) and SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), both in the sarcoidosis group. Direct comparison of sarcoidosis and IPF did not show any differentially regulated genes independent from the statistical methodology. Biological pathway analysis revealed a number of fibrosis-related pathways pronounced in IPF without differences in the regulatory direction. Conclusions: These results demonstrate that FF of end-stage IPF and sarcoidosis lungs, although different in initiation, are similar in gene and protein expression, encouraging further studies on the use of antifibrotic agents in sarcoidosis. MDPI 2022-02-14 /pmc/articles/PMC8870272/ /pubmed/35203313 http://dx.doi.org/10.3390/cells11040664 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kamp, Jan C.
Neubert, Lavinia
Stark, Helge
Hinrichs, Jan B.
Boekhoff, Caja
Seidel, Allison D.
Ius, Fabio
Haverich, Axel
Gottlieb, Jens
Welte, Tobias
Braubach, Peter
Laenger, Florian
Hoeper, Marius M.
Kuehnel, Mark P.
Jonigk, Danny D.
Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis
title Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis
title_full Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis
title_fullStr Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis
title_full_unstemmed Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis
title_short Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis
title_sort comparative analysis of gene expression in fibroblastic foci in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870272/
https://www.ncbi.nlm.nih.gov/pubmed/35203313
http://dx.doi.org/10.3390/cells11040664
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