Transforming growth factor‐β1 stimulates macrophage urokinase expression and release of matrix‐bound basic fibroblast growth factor
Transforming growth factor‐β1 stimulates macrophage urokinase expression and release of matrix‐bound basic fibroblast growth factor
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转化生长因子-β1刺激巨噬细胞尿激酶表达和基质结合碱性成纤维细胞生长因子的释放
DOI：
--
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发表时间：
1993
影响因子：
5.6
通讯作者：
M. Garcia
中科院分区：
文献类型：
--
作者：
D. Falcone;T. McCaffrey;A. Haimovitz;M. Garcia
尿激酶型纤溶酶原激活物（uPA）的巨噬细胞表达似乎在其释放基质结合的碱性成纤维细胞生长因子（bFGF）和转化生长因子-β（TGF-β）中发挥作用。在本文报道的实验中，我们研究了bFGF和TGF-β1对巨噬细胞uPA表达的潜在调节作用。TGF-β1以剂量和时间依赖性方式刺激巨噬细胞系（RAW264.7）分泌的膜和细胞内uPA活性的表达。当在相似浓度下检查时，bFGF几乎没有影响，白细胞介素-1 α、肿瘤坏死因子-α和单核细胞集落刺激因子对巨噬细胞uPA表达没有影响。巨噬细胞暴露于TGF-β1导致uPA mRNA稳态水平快速持续增加，其不依赖于从头蛋白合成，并被放线菌素D完全抑制。然而，TGF-β1诱导的uPA mRNA增加在很大程度上不受随后细胞与放线菌素D孵育的影响。蛋白激酶C抑制剂H7显著降低TGF-β1刺激uPA活性表达的能力。同样，冈田酸和微囊藻毒素，丝氨酸/苏氨酸磷酸酶的抑制剂，增强TGF-β1上调巨噬细胞uPA表达的能力。TGF-β1致敏的细胞几乎将所有添加的纤溶酶原转化为纤溶酶，并表达比对照细胞多6倍的膜结合纤溶酶。TGF-β1与血清或甲胺修饰的α2-巨球蛋白预孵育不影响其诱导巨噬细胞uPA表达的能力。当对照组和TGF-β1致敏的巨噬细胞在含有结合125 I-bFGF的基质上培养时，在纤溶酶原存在的情况下，它们的125 I-bFGF释放分别增加了5倍和10倍。TGF-β诱导巨噬细胞uPA表达的能力和基质结合bFGF的纤溶酶依赖性释放可能提供了TGF-β刺激血管生成的间接机制。© 1993 Wiley利斯公司
Macrophage expression of urokinase‐type plasminogen activator (uPA) appears to play a role in their release of matrix‐bound basic fibroblast growth factor (bFGF) and transforming growth factor‐β (TGF‐β). In experiments reported here, we have examined the potential regulatory effects of bFGF and TGF‐β1 on macrophage uPA expression. TGF‐β1 stimulated in a dose‐ and time‐dependent manner the expression of secreted membrane and intracellular uPA activities by a macrophage cell line (RAW264.7). When examined at similar concentrations, bFGF had little effect, and interleukin‐1α, tumor necrosis factor‐α, and monocyte colony stimulating factor had no effect on macrophage uPA expression. Exposure of macrophages to TGF‐β1 led to a rapid and sustained increase in the steady‐state levels of uPA mRNA that was independent of de novo protein synthesis and was completely inhibited by actinomycin D. However, the TGF‐β1‐induced increase in uPA mRNA was largely unaffected by subsequent incubation of cells with actinomycin D. The protein kinase C inhibitior H7 markedly reduced the ability of TGF‐β1 to stimulate expression of uPA activity. Likewise, okadaic acid and microcystin, inhibitors of serine/threonine phosphatases, potentiated the ability of TGF‐β1 to upregulate macrophage uPA expression. TGF‐β1 primed cells converted nearly all added plasminogen to plasmin and expressed sixfold more membrane‐bound plasmin than control cells. Preincubation of TGF‐β1 with either serum or methylamine‐modified α2‐macroglobulin did not affect its ability to induce macrophage uPA expression. When control and TGF‐β1‐primed macrophages were cultured on matrices containing bound125I‐bFGF, their release of 125I‐bFGF was increased five and tenfold, respectively, in the presence of plasminogen. The ability of TGF‐β to induce macrophage uPA expression and the plasmin‐dependent release of matrix‐bound bFGF may provide an indirect mechanism by which TGF‐β stimulates angiogenesis. © 1993 Wiley‐Liss, Inc.
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血小板血小板反应蛋白与纤溶酶原的复合形成。
DOI：
10.1172/jci111578
发表时间：
1984
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Silverstein,RL;Leung,LL;Harpel,PC;Nachman,RL
通讯作者：
Nachman,RL
影响因子：
56.9
作者：
HEIMARK, RL;TWARDZIK, DR;SCHWARTZ, SM
通讯作者：
SCHWARTZ, SM
聚阴离子对巨噬细胞尿激酶表达的刺激是蛋白激酶 C 依赖性的，并且需要蛋白质和 RNA 合成。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Falcone,DJ;McCaffrey,TA;Vergilio,JA
通讯作者：
Vergilio,JA
影响因子：
15.9
作者：
LYNCH, SE;COLVIN, RB;ANTONIADES, HN
通讯作者：
ANTONIADES, HN
DOI：
--
发表时间：
1992-06
期刊：
The American journal of pathology
影响因子：
--
作者：
G. Pierce;J. Tarpley;D. Yanagihara;Thomas A. Mustoe, MD, FACS;G. M. Fox;A. Thomason
通讯作者：
G. Pierce;J. Tarpley;D. Yanagihara;Thomas A. Mustoe, MD, FACS;G. M. Fox;A. Thomason