Morphologic and mitogenic responses of rabbit synovial fibroblasts to transforming growth factor beta require transforming growth factor alpha or epidermal growth factor.

Morphologic and mitogenic responses of rabbit synovial fibroblasts to transforming growth factor beta require transforming growth factor alpha or epidermal growth factor.
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兔滑膜成纤维细胞对转化生长因子β的形态和有丝分裂反应需要转化生长因子α或表皮生长因子。

DOI:
10.1002/art.1780261110
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发表时间:
1983
影响因子:
--
通讯作者:
Brinckerhoff,CE
Brinckerhoff,CE
中科院分区:
--
文献类型:
--
作者:
Brinckerhoff,CE

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我们检验了正常滑膜成纤维细胞可能响应转化生长因子(TGF)而增殖的假设,TGF是用酸乙醇从牛肾或唾液腺中提取的肽,可引起正常细胞的锚定非依赖性生长。在存在TGF-β的情况下,将10%胎牛血清中的兔滑膜成纤维细胞融合单层暴露于部分纯化的TGF-β 72小时,3 H-胸苷掺入、蛋白含量和细胞数量增加2 - 5倍。在存在表皮生长因子(EGF)(TGF-β的一种)的情况下,使用高压液相色谱纯化的TGF-β获得了类似的结果。纯化的TGF-β本身不具有促有丝分裂作用,它完全依赖于EGF。然而,只有TGF-β沿着EGF,而不是单独的EGF,才会引起显着的形态变化:细胞堆积成病灶,类似于类风湿性滑膜细胞原代培养物中常见的病灶。由TGF-β-EGF组合诱导的促有丝分裂反应被全反式维甲酸阻止,但不被吲哚美辛或地塞米松阻止。这些数据表明,TGF-β,一种从正常细胞中提取的肽,可以与EGF协同作用,导致滑膜细胞的增殖和堆积,并提高了这些因子在类风湿性关节炎和其他增殖性但非恶性疾病中发挥作用的可能性。
We tested the hypothesis that normal synovial fibroblasts might proliferate in response to transforming growth factors (TGFs), peptides that are extracted with acid‐ethanol from bovine kidney or salivary gland and that cause anchorage‐independent growth of normal cells. A 72‐hour exposure of confluent monolayers of rabbit synovial fibroblasts in 10% fetal calf serum to partially purified TGF‐β in the presence of TGF‐β gave a 2‐ to 5‐fold increase in incorporation of3H‐thymidine, protein content, and cell number. Similar results were obtained with high pressure liquid chromatography‐purified TGF‐β in the presence of epidermal growth factor (EGF) (a type of TGF‐β). By itself, purified TGF‐β was not mitogenic; it depended absolutely on EGF. However, only TGF‐β along with EGF, and not EGF alone, induced a marked morphologic change: a piling up of cells into foci resembling those commonly seen in primary cultures of rheumatoid synovial cells. Mitogenic responses induced by the TGF‐β‐EGF combination were prevented by all‐trans‐retinoic acid but not by indomethacin or dexamethasone. The data indicate that TGF‐β, a peptide extracted from normal cells, can act in concert with EGF to cause proliferation and piling up of synovial cells and raise the possibility that these factors may play a role in rheumatoid arthritis and other proliferative but nonmalignant diseases as well.