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, α-smooth muscle actin, and β-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.
Scientific reports. 2019 Dec 30*** epublish ***
Junya Hata, Takeshi Machida, Kanako Matsuoka, Seiji Hoshi, Hidenori Akaihata, Hiroyuki Hiraki, Toshiyuki Suzuki, Soichiro Ogawa, Masao Kataoka, Nobuhiro Haga, Kei Ishibashi, Yoshimi Homma, Hideharu Sekine, Yoshiyuki Kojima
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan. ., Department of Immunology, Fukushima Medical University School of qwMedicine, Fukushima, 960-1295, Japan., Department of Urology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan., Department of Biomolecular Science Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.