June 2013 Research Spotlight : Jagirdar and Zolak

The June 2013 Research Spotlight features two first co-authors:

JagirdarMr Jagirdar holds a M Sc in Biotechnology and M S in Cellular and Molecular Biology. He has developed his career through research as Research assistant/Associate during 2004-2012 in part at University of Michigan. During his time at UAB Mr Jagirdar was instrumental in augmenting pleural research with an emphasis on dissecting the role of the pleural mesothelial compartment in the etiology of Idiopathic Pulmonary Fibrosis. Mr Jagirdar left UAb in Dec 2011 and now runs Geneclick.org, a non profit Bioinformatics & Computational Biology service.

 Dr. Jason Zolak received his B.S. degree in neurobiology and physiology from the University of Maryland, and his medical degree from the ZolakUniversity of Virginia. He completed a surgery internship, followed by an internal medicine residency at UAB in 2010. He will complete his fellowship in pulmonary and critical care medicine in June of 2013. Dr. Zolak has a clinical interest in pleural disease and malignancy. In conjunction with Dr. Veena Antony, he has investigated the role of pleural mesothelial cells in fibrogenic lung injury. They have demonstrated the novel finding that pleural mesothelial cells undergo differentiation with acquisition of mesenchymal phenotypic characteristics and migrate into the lung parenchyma in fibrogenic lung injury. They have further elucidated a potentially protective role for the induction of heme oxygenase-1 in idiopathic pulmonary fibrosis. They continue to investigate the role of pleural-based therapies for parenchymal diseases.

Abstract

The origin of the myofibroblast in fibrotic lung disease is uncertain, and no effective medical therapy for fibrosis exists. We have previously demonstrated that transforming growth factor-β1 (TGF-β1) induces pleural mesothelial cell (PMC) transformation into myofibroblasts and haptotactic migration in vitro. Whether PMC differentiation and migration occurs in vivo, and whether this response can be modulated for therapeutic benefit, is unknown. Here, using mice recombinant for green fluorescent protein (GFP) driven by the Wilms tumor-1 (WT-1) promoter, we demonstrate PMC trafficking into the lung and differentiation into myofibroblasts. Carbon monoxide or the induction of heme oxygenase-1 (HO-1) inhibited the expression of myofibroblast markers, contractility, and haptotaxis in PMCs treated with TGF-β1. Intrapleural HO-1 induction inhibited PMC migration after intratracheal fibrogenic injury. PMCs from patients with idiopathic pulmonary fibrosis (IPF) exhibited increased expression of myofibroblast markers and enhanced contractility and haptotaxis, compared with normal PMCs. Carbon monoxide reversed this IPF PMC profibrotic phenotype. WT-1-expressing cells were present within fibrotic regions of the lungs in IPF subjects, supporting a role for PMC differentiation and trafficking as contributors to the myofibroblast population in lung fibrosis. Our findings also support a potential role for pleural-based therapies to modulate pleural mesothelial activation and parenchymal fibrosis progression.

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