title: Matrix association of latent TGF-beta binding protein-2 (LTBP-2) is dependent on fibrillin-1.
abstract: The components of the extracellular matrix (ECM) and their differential expression patterns play important roles in tissue formation. The deposition of latent TGF-beta binding proteins (LTBPs) to the ECM exhibit distinct distribution profiles. We have analyzed here the temporal and spatial ECM association of latent TGF-beta binding protein LTBP-2 in cultured human embryonic lung fibroblasts. We found that LTBP-2 was not assembled to the ECM until by confluency of cultures following the deposition of fibronectin (FN) and fibrillin-1. In 5-day-old cultures LTBP-2 was rapidly secreted from cells and it subsequently associated with the ECM as shown by metabolic labeling and immunoprecipitation. LTBP-2 colocalized transiently with fibronectin and failed to assemble to the ECM of FN deficient mouse fibroblasts. Analysis of different cultured human cell lines revealed partial colocalization of LTBP-2 and fibrillin-1 in the ECM of fibroblasts, MG-63 osteosarcoma cells and human vascular endothelial cells. Silencing of fibrillin-1 expression by lentiviral shRNAs profoundly disrupted the deposition of LTBP-2. Current results suggest that LTBP-2 is not an element of the provisional ECM of fibroblasts but is more likely a component of more mature ECM and indicate that matrix association of LTBP-2 depends on a pre-formed fibrillin-1 network.
authors.affiliation: Departments of Pathology and Virology, Haartman Institute and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Piia
authors.initials: P
authors.lastname: Vehviläinen
authors.forename: Marko
authors.initials: M
authors.lastname: Hyytiäinen
authors.forename: Jorma
authors.initials: J
authors.lastname: Keski-Oja
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D034622:RNA Interference; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse; C509035:LTBP2 protein, human