TGF-α and ErbB2 production in synovial joint tissue:: increased expression in arthritic joints

TGF-α and ErbB2 production in synovial joint tissue:: increased expression in arthritic joints
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DOI:
10.1080/03009740510017715
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发表时间:
2005-06-01
影响因子:
2.1
通讯作者:
Wasteson, Å
Wasteson, Å
中科院分区:
医学4区
文献类型:
--
作者:
Hallbeck, AL;Walz, TM;Wasteson, Å

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目的:已知滑膜组织和滑膜炎症过程中存在的细胞类型在体外可产生表皮生长因子受体(EGFR)/ErbB-1/HER-1和强大的EGFR配体转化生长因子-α(TGF-α)。同时表达的转化生长因子-α、表皮生长因子受体和ErbB2在体外和体内都有很强的增殖驱动力。然而,在活体关节组织中是否存在转化生长因子-α和EGFR/EGFR-配体家族成员还没有得到彻底的研究。目的:探讨人关节滑膜组织中是否存在转化生长因子-α(TGF-α)、表皮生长因子受体(EGFR)和ErbB2的表达,尤其是在类风湿关节炎(RA)发病过程中。方法:采用免疫组织化学方法检测23例RA患者、8例其他关节炎患者、2例骨关节炎(OA)患者和6例创伤后患者(对照组)膝关节滑液中的TGF-α蛋白表达。应用原位杂交和免疫组织化学方法检测6例RA/2 OA/6对照膝关节滑膜组织中的转化生长因子-αmRNA及转化生长因子-α、ErbB2、EGFR和CD68的表达。采用逆转录-聚合酶链式反应(RT-PCR)和/或Northern印迹技术检测滑膜细胞中转化生长因子-α的表达。结果:在滑膜和大部分滑膜组织中均有表达。转化生长因子-α水平显著高于对照组(P<0.05)。
Objective: Cell types present in synovial joint tissues and during synovitis are known to produce epidermal growth factor receptor ( EGFR)/ErbB-1/HER-1 and the potent EGFR-ligand transforming growth factor-alpha (TGF-alpha) in vitro. Concomitant expression of TGF-alpha, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF-alpha and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-alpha, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis ( RA).Methods: TGF-alpha protein was immunodetected in knee synovial fluid ( SF) collected from 23 RA patients, eight patients with other arthritic conditions, two osteoarthritis ( OA) patients, and six post-traumatic patients ( control). TGF-alpha mRNA and TGF-alpha, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF-alpha mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique.Results: TGF-alpha protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF-alpha levels were significantly higher (p