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PMID:9008713
| Citation |
Nakajima, Y, Miyazono, K, Kato, M, Takase, M, Yamagishi, T and Nakamura, H (1997) Extracellular fibrillar structure of latent TGF beta binding protein-1: role in TGF beta-dependent endothelial-mesenchymal transformation during endocardial cushion tissue formation in mouse embryonic heart. J. Cell Biol. 136:193-204 |
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| Abstract |
Transforming growth factor-beta (TGF beta) is a dimeric peptide growth factor which regulates cellular differentiation and proliferation during development. Most cells secrete TGF beta as a large latent TGF beta complex containing mature TGF beta, latency associated peptide, and latent TGF beta-binding protein (LTBP)-1. The biological role of LTBP-1 in development remains unclear. Using a polyclonal antiserum specific for LTBP-1 (Ab39) and three-dimensional collagen gel culture assay of embryonic heart, we examined the tissue distribution of LTBP-1 and its functional role during the formation of endocardial cushion tissue in the mouse embryonic heart. Mature TGF beta protein was required at the onset of the endothelial-mesenchymal transformation to initiate endocardial cushion tissue formation. Double antibody staining showed that LTBP-1 colocalized with TGF beta 1 as an extracellular fibrillar structure surrounding the endocardial cushion mesenchymal cells. Immunogold electronmicroscopy showed that LTBP-1 localized to 40-100 nm extracellular fibrillar structure and 5-10-nm microfibrils. The anti-LTBP-1 antiserum (Ab39) inhibited the endothelial-mesenchymal transformation in atrio-ventricular endocardial cells cocultured with associated myocardium on a three-dimensional collagen gel lattice. This inhibitory effect was reversed by administration of mature TGF beta proteins in culture. These results suggest that LTBP-1 exists as an extracellular fibrillar structure and plays a role in the storage of TGF beta as a large latent TGF beta complex. |
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| Keywords |
Animals; Antibody Specificity; COS Cells; Carrier Proteins/analysis; Carrier Proteins/physiology; Coculture Techniques; Culture Techniques; Endocardium/cytology; Endocardium/growth & development; Endothelium, Vascular/embryology; Extracellular Matrix/chemistry; Fibrinolysin; Heart/embryology; Humans; Intracellular Signaling Peptides and Proteins; Latent TGF-beta Binding Proteins; Mesoderm/cytology; Mice; Mice, Inbred ICR; Myocardium/chemistry; Myocardium/cytology; Transfection; Transforming Growth Factor beta/analysis; Transforming Growth Factor beta/pharmacology |
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