Davila Hugo H, Magee Thomas R, Zuniga Freddi I, Rajfer Jacob, Gonzalez-Cadavid Nestor F
Department of Urology, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA.
Urology. 2005 Apr;65(4):645-8. doi: 10.1016/j.urology.2005.01.010.
To investigate whether tissue expression of plasminogen activator inhibitor type 1 (PAI-1) is increased in the fibrotic plaque of human Peyronie's disease (PD). Increased tissue levels of PAI-1, an inhibitor of both fibrinolysis and collagenolysis, have been found in a variety of fibrotic conditions. Recently, it was reported that PAI-1 expression was also increased in the fibrotic plaque of an animal model of PD induced by the injection of fibrin into the tunica albuginea (TA) of the penis.
Tissue (n = 10/group) and cells (n = 4/group) obtained from the penile TA plaque of patients with PD or from normal TA were subjected to RNA extraction and real-time reverse transcriptase-polymerase chain reaction. Tissues were also analyzed by immunohistochemistry (n = 8/group) for the detection of PAI-1 expression at the transcription and protein levels.
A significant 3.5-fold to 16-fold increase was found in both PAI-1 mRNA and protein levels in the human PD plaque and the respective fibroblast cultures compared with the normal non-PD TA.
The observed increase in PAI-1 in the human PD plaque agrees with what has been observed in the rat and suggests that PAI-1 may be a key pro-fibrotic factor in the development of human PD.
研究1型纤溶酶原激活物抑制剂(PAI-1)的组织表达在人类佩罗尼氏病(PD)的纤维化斑块中是否增加。在多种纤维化疾病中已发现,作为纤维蛋白溶解和胶原溶解的抑制剂,PAI-1的组织水平升高。最近有报道称,在通过向阴茎白膜(TA)注射纤维蛋白诱导的PD动物模型的纤维化斑块中,PAI-1的表达也增加。
从PD患者的阴茎TA斑块或正常TA获取组织(每组n = 10)和细胞(每组n = 4),进行RNA提取和实时逆转录-聚合酶链反应。还通过免疫组织化学(每组n = 8)对组织进行分析,以检测转录和蛋白质水平的PAI-1表达。
与正常非PD的TA相比,在人类PD斑块和相应的成纤维细胞培养物中,PAI-1的mRNA和蛋白质水平均显著增加了3.5倍至16倍。
在人类PD斑块中观察到的PAI-1增加与在大鼠中观察到的情况一致,表明PAI-1可能是人类PD发展中的关键促纤维化因子。