Global Gene Expression Analysis in an in vitro Fibroblast Model of Idiopathic Pulmonary Fibrosis Reveals Potential Role for CXCL14/CXCR4

Date

2018

Authors

Rodriguez, Luis R.
Emblom-Callahan, Margaret
Chhina, Mantej
Bui, Sarah
Aljeburry, Bilal

Journal Title

Journal ISSN

Volume Title

Publisher

Scientific Reports

Abstract

Idiopathic Pulmonary Fibrosis (IPF) is a progressive disorder that is marked by an over accumulation of activated fibroblast populations. Despite the improved understanding of many mechanisms within this disease, global gene expression analysis has few focused studies on the fibroblast, the central effector cell of progressive fibrosis. We present a unique analysis of IPF pulmonary fibroblasts as they transition through cell culture and identify in vitro altered cellular processes. Fibroblasts were isolated from diseased (n = 8) and non-diseased (n = 4) lungs. Global gene expression analysis was carried out at the initial point of isolation and after 3 weeks of culture. We identify several genes that are altered by removal of the fibroblast from the IPF environment. Comparison of this subset of genes to four previously published whole lung analyses refined our list to a small subset of key fibroblast specific genes important in IPF. Application of STRING database analysis and confirmation via in-vitro and histological assay highlights the CXCL14/CXCR4 chemokine axis with a possible role in the progression and/or activation of fibroblasts within the IPF lung. Our findings, present a possible therapeutic target for IPF and a model for the study and discovery of novel protein and processes in this terrible disease.

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Citation

Rodriguez, Luis R., Margaret Emblom-Callahan, Mantej Chhina, Sarah Bui, Bilal Aljeburry, Luc H. Tran, Rebecca Novak, Merte Lemma, Steven D. Nathan, and Geraldine M. Grant. "Global Gene Expression Analysis in an in vitro Fibroblast Model of Idiopathic Pulmonary Fibrosis Reveals Potential Role for CXCL14/CXCR4." Scientific Reports 8, no. 1 (2018): 3983.