Novel differences in gene expression and functional capabilities of myofibroblast populations in idiopathic pulmonary fibrosis

Walsh, S. M., Worrell, J. C. , Fabre, A., Hinz, B., Kane, R. and Keane, M. P. (2018) Novel differences in gene expression and functional capabilities of myofibroblast populations in idiopathic pulmonary fibrosis. American Journal of Physiology: Lung Cellular and Molecular Physiology, 315(5), L697-L710. (doi: 10.1152/ajplung.00543.2017) (PMID:30091381)

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Abstract

Idiopathic pulmonary fibrosis (IPF), a chronic progressive interstitial pneumonia, is characterized by excessive fibroproliferation. Key effector cells in IPF are myofibroblasts that are recruited from three potential sources: resident fibroblasts, fibrocytes, and epithelial cells. We hypothesized that IPF myofibroblasts from different sources display unique gene expression differences and distinct functional characteristics. Primary human pulmonary fibroblasts (normal and IPF), fibrocytes, and epithelial cells were activated using the profibrotic factors TGF-β and TNF-α. The resulting myofibroblasts were characterized using cell proliferation, soluble collagen, and contractility assays, ELISA, and human fibrosis PCR arrays. Genes of significance in human whole lung were validated by immunohistochemistry on human lung sections. Fibroblast-derived myofibroblasts exhibited the greatest increase in expression of profibrotic genes and genes involved in extracellular matrix remodeling and signal transduction. Functional studies demonstrated that myofibroblasts derived from fibrocytes expressed mostly soluble collagen and chemokine (C-C) motif ligand (CCL) 18 but were the least proliferative of the myofibroblast progeny. Activated IPF fibroblasts displayed the highest levels of contractility and CCL2 production. This study identified novel differences in gene expression and functional characteristics of different myofibroblast populations. Further investigation into the myofibroblast phenotype may lead to potential therapeutic targets in future IPF research.

Item Type:Articles
Additional Information:J. C. Worrell was supported by the Molecular Medicine Ireland Clinical and Translational Research Scholars Programme, funded under PRTLI Cycle 5 ERDF. B. Hinz is supported by Canadian Institutes of Health Research Foundation Grant 375597.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Worrell, Dr Julie
Authors: Walsh, S. M., Worrell, J. C., Fabre, A., Hinz, B., Kane, R., and Keane, M. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:American Journal of Physiology: Lung Cellular and Molecular Physiology
Publisher:American Physiological Society
ISSN:1040-0605
ISSN (Online):1522-1504
Published Online:22 October 2018

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