Insulin-like growth factor binding proteins 3 and 5 are overexpressed in idiopathic pulmonary fibrosis and contribute to extracellular matrix deposition.
Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown etiology that results in significant morbidity and mortality. The pathogenesis of IPF is not completely understood. Because recent studies have implicated insulin-like growth factor-I (IGF-I) in the pathogenesis of fibrosis, we examined the expression and function of insulin-like growth factor binding proteins (IGFBP)-3 and -5 in IPF. IGFBP-3 and -5 levels were increased in vivo in IPF lung tissues and in vitro in fibroblasts cultured from IPF lung. The IGFBPs secreted by IPF fibroblasts are functionally active and can bind IGF-I, and IGFBPs secreted by primary fibroblasts bind extracellular matrix components. Our results also suggest that IGFBPs may be involved in the initiation and/or perpetuation of fibrosis by virtue of their ability to induce the production of extracellular matrix components such as collagen type I and fibronectin in normal primary adult lung fibroblasts. Although transforming growth factor-beta increased IGFBP-3 production by primary fibroblasts in a time-dependent manner, IGFBP-5 levels were not increased by transforming growth factor-beta. Taken together, our results suggest that IGFBPs play an important role in the development of fibrosis in IPF.
Pilewski
Joseph M
JM
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Montefiore 628 NW, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA.
Liu
Lixin
L
Henry
Adam C
AC
Knauer
Alycia V
AV
Feghali-Bostwick
Carol A
CA
D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis*; D008024:Ligands; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012260:Ribonucleases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018076:DNA, Complementary; D005353:Fibronectins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D008024:Ligands; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen; D012260:Ribonucleases