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.
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.
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DOI：
10.1083/jcb.123.5.1249
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发表时间：
1993-12
期刊：
影响因子：
--
通讯作者：
Tamaoki T
中科院分区：
文献类型：
--
作者：
Sato Y;Okada F;Abe M;Seguchi T;Kuwano M;Sato S;Furuya A;Hanai N;Tamaoki T
转化生长因子- β (tgf - β)在内皮细胞和平滑肌细胞共培养过程中以潜伏形式分泌并激活。在共培养过程中，潜伏tgf - β (ltgf - β)的激活需要位于内皮细胞表面的纤溶蛋白，而ltgf - β的激活需要靶向细胞表面。本研究探讨了LTGF- β的细胞靶向性。我们检测了从人血小板中分离的125i大LTGF- β 1与平滑肌细胞的特异性结合，而不是与内皮细胞的特异性结合。针对大LTGF- β 1复合物的潜伏期相关肽（LAP）的单抗抑制了125i大LTGF- β 1与平滑肌细胞的结合，在共培养过程中抑制了LTGF- β的激活。125I-large ltgf - β 1的结合不能被甘露糖-6-磷酸（300微克/毫升）或合成肽Arg-Gly-Asp-Ser（300微克/毫升）所竞争。这些结果表明，在内皮细胞和平滑肌细胞共培养过程中，ltgf - β的激活需要将ltgf - β靶向平滑肌细胞。ltgf - β靶向平滑肌细胞是由LAP介导的，而LAP负责靶向平滑肌细胞的结构域可能与甘露糖-6-磷酸或Arg-Gly-Asp序列无关，而这两种结构域之前都被认为是LAP的细胞结合结构域的候选结构域。
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.