Novel Myofibroblast Differences in Idiopathic Pulmonary Fibrosis
Investigations by Prof Michael Keane’s group into the genetic profiles and functional characteristics of different myofibroblasts types has confirmed significant inter-population variability. The St Vincent’s University Hospital research group hope that these differences might lead to potential therapeutic targets in idiopathic pulmonary fibrosis (IPF).
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia that is characterized by excessive fibroproliferation. Myofibroblasts are key effector cells in IPF that are recruited from three potential sources: resident fibroblasts, fibrocytes and epithelial cells. The investigators hypothesized that IPF myofibroblasts from these different sources of origin might display unique genetic profiles and distinct functional characteristics.
The group activated primary human pulmonary fibroblasts (normal and IPF), fibrocytes and epithelial cells into myofibroblasts using the pro fibrotic factors TGF β and TNF α and characterised the resulting myofibroblasts using cell proliferation, soluble collagen, ELISA and contractility assays, and human fibrosis PCR arrays. They also validated genes of significance in whole human lung and by immunohistochemistry on human lung sections.
Fibroblast-derived myofibroblasts exhibited the highest expression increase in pro fibrotic genes, and genes involved in extracellular matrix remodelling and signal transduction. Functional studies demonstrated that myofibroblasts derived from fibrocytes expressed most soluble collagen and CCL18 but were least proliferative of all myofibroblast progeny. Activated IPF fibroblasts displayed highest contraction and highest levels of CCL2 production.
This study published in the American Journal of Physiology – Lung Cellular and Molecular Physiology has identified novel differences in both gene expression and functional characteristics in different myofibroblast populations. Further investigation into the myofibroblast phenotype may lead to potential therapeutic targets in the future field of IPF research.
Novel Differences in Gene Expression and Functional Capabilities of Myofibroblast Populations in Idiopathic Pulmonary Fibrosis
Sinead M Walsh, Julie C Worrell, Aurelie Fabre, Boris Hinz, Rosemary Kane, and Michael P Keane