Pigment epithelium–derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis

GP Cosgrove, KK Brown, WP Schiemann… - American journal of …, 2004 - atsjournals.org
GP Cosgrove, KK Brown, WP Schiemann, AE Serls, JE Parr, MW Geraci, MI Schwarz…
American journal of respiratory and critical care medicine, 2004atsjournals.org
Pigment epithelium-derived factor (PEDF) is a 50-kD protein with angiostatic and
neurotrophic activities that regulates vascular development within the eye. PEDF expression
was increased in the lungs of patients with idiopathic pulmonary fibrosis (IPF) based on
microarray analyses. Angiogenesis has been implicated in the pathogenesis of fibrotic lung
diseases, we therefore hypothesized that regional abnormalities in vascularization occur in
IPF as a result of an imbalance between PEDF and vascular endothelial growth factor. We …
Pigment epithelium-derived factor (PEDF) is a 50-kD protein with angiostatic and neurotrophic activities that regulates vascular development within the eye. PEDF expression was increased in the lungs of patients with idiopathic pulmonary fibrosis (IPF) based on microarray analyses. Angiogenesis has been implicated in the pathogenesis of fibrotic lung diseases, we therefore hypothesized that regional abnormalities in vascularization occur in IPF as a result of an imbalance between PEDF and vascular endothelial growth factor. We demonstrated that vascular density is regionally decreased in IPF within the fibroblastic foci, and that within these areas PEDF was increased, whereas vascular endothelial growth factor was decreased. PEDF colocalized with the fibrogenic cytokine, transforming growth factor (TGF)-β1, particularly within the fibrotic interstitium and the fibroblastic focus, and prominently within the epithelium directly overlying the fibroblastic focus. This suggested that TGF-β1 might regulate PEDF expression. Using 3T3-L1 fibroblasts and human lung fibroblasts, we showed that PEDF was indeed a TGF-β1 target gene. Collectively, our findings implicate PEDF as a regulator of pulmonary angiogenesis and an important mediator in IPF.
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