Complement activation by autoantigen recognition in the growth process of benign prostatic hyperplasia
Complement activation by autoantigen recognition in the growth process of benign prostatic hyperplasia
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DOI：
10.1038/s41598-019-57001-w
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发表时间：
2019-12-30
影响因子：
4.6
通讯作者：
Kojima, Yoshiyuki
中科院分区：
文献类型：
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作者：
Hata, Junya;Machida, Takeshi;Kojima, Yoshiyuki
良性前列腺增生（BPH）的病理生理机制尚不清楚。在这里，我们集中在前列腺增生症的生长使用大鼠模型中的补体激活。在大鼠泌尿生殖窦植入后，从大鼠中收获BPH组织。采用实时荧光定量RT-PCR、免疫印迹和免疫组织化学方法检测大鼠和人BPH组织中C1 q、C3、甘露糖结合凝集素（MBL）、B因子（FB）和C5 B-9的表达和沉积水平。通过ELISA分析大鼠BPH模型中的血清IgG水平，并使用IHC评估组织定位。用免疫沉淀法分离BPH大鼠血清IgG自身抗体结合蛋白。与正常组织相比，C1 q、C3、MBL、FB和C5 b-9在大鼠BPH组织中高度定位。与此相反，C3，FB和C5 b-9，而不是C1 q和MBL，大量检测到人类BPH组织相比，正常组织。在BPH大鼠组织中发现IgG的弥漫性定位，热休克蛋白90、膜联蛋白、α-平滑肌肌动蛋白和β-肌动蛋白被鉴定为BPH模型中IgG自身抗体的靶点。我们的研究结果有力地表明了补体激活在BPH生长过程中的作用，可能是由自身抗体的经典途径激活触发的。
The pathophysiology of benign prostatic hyperplasia (BPH) remained unclear. Here, we concentrated on the complement activation in the growth of BPH using a rat model. BPH tissues were harvested from rats after rat urogenital sinus implantation. The local expression and deposition levels of C1q, C3, mannose-binding lectin (MBL), factor B (FB), and C5b-9 in the rat and human BPH tissues were analyzed by real-time RT-PCR, western blotting and immunohistochemistry (IHC). Serum IgG levels in the rat BPH model were analyzed by ELISA, and IHC was used to assess tissue localization. Proteins binding serum IgG autoantibody in the BPH rats were isolated by immunoprecipitation. C1q, C3, MBL, FB and C5b-9 were highly localized in rat BPH tissues compared to normal tissues. In contrast, C3, FB and C5b-9, but not C1q and MBL, were abundantly detected in human BPH tissues compared to normal tissues. Diffuse localization of IgG in rat BPH tissues was found. Heat shock protein 90, annexin, alpha-smooth muscle actin, and beta-actin were identified as targets for IgG autoantibodies in the BPH model. Our results strongly suggested the role for complement activation in the growth process of BPH, likely triggered by classical pathway activation with autoantibodies.