Decreased type II type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions - Conversion from an antiproliferative to profibrotic response to TGF-beta 1
Decreased type II type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions - Conversion from an antiproliferative to profibrotic response to TGF-beta 1
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DOI：
10.1172/jci118333
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发表时间：
1995-12-01
影响因子：
15.9
通讯作者：
Bush, HL
中科院分区：
文献类型：
--
作者：
McCaffrey, TA;Consigli, S;Bush, HL
动脉粥样硬化和血管成形术后再狭窄可能是由伤口愈合异常引起的。目前的研究报告称，正常人平滑肌细胞的生长受到 TGF-β1（一种有效的伤口愈合剂）的抑制，并且几乎不诱导胶原蛋白合成到 TGF-β1，然而从人血管病变中生长的细胞受到 TGF-β1 的生长刺激，并显着增加胶原蛋白的合成。两种细胞类型都会增加纤溶酶原激活剂抑制剂-1 的产生，改变肌动蛋白表型I-125-TGF-β1 膜交联表明正常人平滑肌细胞表达 I、II、III 型受体，病灶细胞中 II 型受体显着减少，I 型或 III 型受体变化不大，RT-PCR 证实病灶细胞中 LI 型 TGF-β1 受体 mRNA 减少，II 型受体转染进入病变细胞可恢复对 TGF-P1 的生长抑制反应，这意味着信号传导保持响应。由于 TGF-P1 在纤维增生性血管病变中过度表达，受体变异细胞将被允许以缓慢但不受控制的方式生长，同时过量产生细胞外基质成分。这种 TGF-β1 受体功能障碍可能与动脉粥样硬化、再狭窄和相关纤维增生性疾病有关。
Atherosclerosis and postangioplasty restenosis may result from abnormal wound healing, The present studies report that normal human smooth muscle cells are growth inhibited by TGF-beta 1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta 1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta 1 and markedly increase collagen synthesis, Both cell types increase plasminogen activator inhibitor-1 production, switch actin phenotypes in response to TGF-beta 1, and produce similar levels of TGF-P activity, Membrane cross-linking of I-125-TGF-beta 1 indicates that normal human smooth muscle cells express type I, II, and III receptors, The type II receptor is strikingly decreased in lesion cells, with little change in the type I or III receptors, RT-PCR confirmed that the type LI TGF-beta 1 receptor mRNA is reduced in lesion cells, Transfection of the type II receptor into lesion cells restores the growth inhibitory response to TGF-P1, implying that signaling remains responsive, Because TGF-P1 is overexpressed in fibroproliferative vascular lesions, receptor-variant cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components, This TGF-beta 1 receptor dysfunction may be relevant for atherosclerosis, restenosis, and related fibroproliferative diseases.