The mechanism for the activation of latent TGF-beta during co-culture of endothelial cells and smooth muscle cells: cell-type specific targeting of latent TGF-beta to smooth muscle cells

doi:10.1083/jcb.123.5.1249

This Article

	Full Text (PDF, 671K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Sato, Y.
	Articles by Tamaoki, T.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Sato, Y.
	Articles by Tamaoki, T.


Social Bookmarking

	What's this?

ARTICLES

The mechanism for the activation of latent TGF-beta during co-culture of endothelial cells and smooth muscle cells: cell-type specific targeting of latent TGF-beta to smooth muscle cells

Y Sato, F Okada, M Abe, T Seguchi, M Kuwano, S Sato, A Furuya, N Hanai and T Tamaoki
Department of Internal Medicine 1, Oita Medical University, Japan.

Transforming growth factor-beta (TGF-beta) is secreted in a latent form and activated during co-culture of endothelial cells and smooth muscle cells. Plasmin located on the surface of endothelial cells is required for the activation of latent TGF-beta (LTGF-beta) during co-culture, and the targeting of LTGF-beta to the cellular surface is requisite for its activation. In the present study, the cellular targeting of LTGF- beta was examined. We detected the specific binding of 125I-large LTGF- beta 1 isolated from human platelets to smooth muscle cells but not to endothelial cells. A mAb against the latency-associated peptide (LAP) of large LTGF-beta 1 complex, which blocked the binding of 125I-large LTGF-beta 1 to smooth muscle cells, inhibited the activation of LTGF- beta during co-culture. The binding of 125I-large LTGF-beta 1 could not be competed either by mannose-6-phosphate (300 microM) or by the synthetic peptide Arg-Gly-Asp-Ser (300 micrograms/ml). These results indicate that the targeting of LTGF-beta to smooth muscle cells is required for the activation of LTGF-beta during co-culture of endothelial cells and smooth muscle cells. The targeting of LTGF-beta to smooth muscle cells is mediated by LAP, and the domain of LAP responsible for the targeting to smooth muscle cells may not be related to mannose-6-phosphate or an Arg-Gly-Asp sequence, both of which have been previously proposed as candidates for the cellular binding domains within LAP.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Webber, J., Meran, S., Steadman, R., Phillips, A. (2009). Hyaluronan Orchestrates Transforming Growth Factor-{beta}1-dependent Maintenance of Myofibroblast Phenotype. J. Biol. Chem. 284: 9083-9092 [Abstract] [Full Text]
Taylor, A. W. (2009). Review of the activation of TGF-{beta} in immunity. J. Leukoc. Biol. 85: 29-33 [Abstract] [Full Text]
Takamura, Y., Tomomatsu, T., Kubo, E., Tsuzuki, S., Akagi, Y. (2008). Role of the Polyol Pathway in High Glucose-Induced Apoptosis of Retinal Pericytes and Proliferation of Endothelial Cells. IOVS 49: 3216-3223 [Abstract] [Full Text]
DeLeve, L. D., Wang, X., Hu, L., McCuskey, M. K., McCuskey, R. S. (2004). Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation. Am. J. Physiol. Gastrointest. Liver Physiol. 287: G757-G763 [Abstract] [Full Text]
Zhang, X. L., Selbi, W., de la Motte, C., Hascall, V., Phillips, A. (2004). Renal Proximal Tubular Epithelial Cell Transforming Growth Factor-{beta}1 Generation and Monocyte Binding. Am. J. Pathol. 165: 763-773 [Abstract] [Full Text]
Fraser, D., Brunskill, N., Ito, T., Phillips, A. (2003). Long-Term Exposure of Proximal Tubular Epithelial Cells to Glucose Induces Transforming Growth Factor-{beta}1 Synthesis via an Autocrine PDGF Loop. Am. J. Pathol. 163: 2565-2574 [Abstract] [Full Text]
Fraser, D., Wakefield, L., Phillips, A. (2002). Independent Regulation of Transforming Growth Factor-{beta}1 Transcription and Translation by Glucose and Platelet-Derived Growth Factor. Am. J. Pathol. 161: 1039-1049 [Abstract] [Full Text]
Parekh, T. V., Gama, P., Wen, X., Demopoulos, R., Munger, J. S., Carcangiu, M.-L., Reiss, M., Gold, L. I. (2002). Transforming Growth Factor {beta} Signaling Is Disabled Early in Human Endometrial Carcinogenesis Concomitant with Loss of Growth Inhibition. Cancer Res. 62: 2778-2790 [Abstract] [Full Text]
McKaig, B. C., Makh, S. S., Hawkey, C. J., Podolsky, D. K., Mahida, Y. R. (1999). Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta 3. Am. J. Physiol. Gastrointest. Liver Physiol. 276: G1087-G1093 [Abstract] [Full Text]
Nakano, N., Morishita, R., Moriguchi, A., Nakamura, Y., Hayashi, S.-i., Aoki, M., Kida, I., Matsumoto, K., Nakamura, T., Higaki, J., Ogihara, T. (1998). Negative Regulation of Local Hepatocyte Growth Factor Expression by Angiotensin II and Transforming Growth Factor-� in Blood Vessels : Potential Role of HGF in Cardiovascular Disease. Hypertension 32: 444-451 [Abstract] [Full Text]
Saharinen, J., Taipale, J., Monni, O., Keski-Oja, J. (1998). Identification and Characterization of a New Latent Transforming Growth Factor-beta -binding Protein, LTBP-4. J. Biol. Chem. 273: 18459-18469 [Abstract] [Full Text]
Ge, R.-L., Kubo, K., Kobayashi, T., Sekiguchi, M., Honda, T. (1998). Blunted hypoxic pulmonary vasoconstrictive response in the rodent Ochotona curzoniae (pika) at high altitude. Am. J. Physiol. Heart Circ. Physiol. 274: H1792-H1799 [Abstract] [Full Text]
Nunes, I., Gleizes, P.-E., Metz, C. N., Rifkin, D. B (1997). Latent Transforming Growth Factor-{beta} Binding Protein Domains Involved in Activation and Transglutaminase-dependent Cross-Linking of Latent Transforming Growth Factor-{beta}. JCB 136: 1151-1163 [Abstract] [Full Text]
Nakajima, Y., Miyazono, K., Kato, M., Takase, M., Yamagishi, T., 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. JCB 136: 193-204 [Abstract] [Full Text]
Farre, A. L., Mosquera, J. R., de Miguel, L. S., Millas, I., de Frutos, T., Monton, M., Sierra, M. P., Riesco, A., Casado, S. (1996). Endothelial Cells Inhibit NO Generation by Vascular Smooth Muscle Cells: Role of Transforming Growth Factor-�. Arterioscler. Thromb. Vasc. Bio. 16: 1263-1268 [Abstract] [Full Text]
Yin, W., Smiley, E., Germiller, J., Mecham, R. P., Florer, J. B., Wenstrup, R. J., Bonadio, J. (1995). Isolation of a Novel Latent Transforming Growth Factor-[IMAGE] Binding Protein Gene (LTBP-3). J. Biol. Chem. 270: 10147-10160 [Abstract] [Full Text]
Taipale, J., Lohi, J., Saarinen, J., Kovanen, P. T., Keski-Oja, J. (1995). Human Mast Cell Chymase and Leukocyte Elastase Release Latent Transforming Growth Factor-beta1 from the Extracellular Matrix of Cultured Human Epithelial and Endothelial Cells. J. Biol. Chem. 270: 4689-4696 [Abstract] [Full Text]
Wells, J., Strickland, S (1994). Aprotinin, a Kunitz-type protease inhibitor, stimulates skeletal muscle differentiation. Development 120: 3639-3647 [Abstract]