Complement activation by autoantigen recognition in the growth process of benign prostatic hyperplasia

Junya Hata,Soichiro Ogawa,Yoshiyuki Kojima,Masao Kataoka,Kanako Matsuoka,Hideharu Sekine,Nobuhiro Haga,Hidenori Akaihata,Hiroyuki Hiraki,Yoshimi Homma,Toshiyuki Suzuki,Takeshi Machida,Kei Ishibashi,Seiji Hoshi

doi:10.1038/s41598-019-57001-w

Junya Hata, Soichiro Ogawa + Show 12 more

Open Access

https://doi.org/10.1038/s41598-019-57001-w

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Journal: Scientific Reports	Publication Date: Dec 1, 2019
Citations: 10	License type: open-access

Affiliation: Fukushima Medical University

Abstract

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.

Highlights

The pathophysiology of benign prostatic hyperplasia (BPH) remained unclear
The expression levels of Cfb were higher in the rat BPH tissues than controls; statistical significance was not reached at any time point tested
Our results suggest that the growth of BPH lesions in rat BPH tissue was initiated by activation of the classical pathway by the binding of C1q to antigen-antibody complexes, with subsequent activation of the lectin pathway and the alternative pathway

Summary

Introduction

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. The cause of inflammation could include infection, mechanical stimulation, hormonal change, and autoimmunity[3,4,5] How these factors are responsible for the pathogenesis of BPH remains unclear. Functional network analysis in the study showed that the gene expression of C1qa, C1qb, C1qc, C1r, and C2, the complement components of the classical pathway, were significantly increased, and the expression of Cd59, the major cell surface inhibitor of C5b-9 formation, was significantly decreased in the BPH tissue of the BPH rat model compared to their normal prostate tissue[9]. To clarify the involvement of complement activation in the mechanism of BPH growth, we analyzed the expression and deposition of complement components, including the classical pathway, in prostate tissue of BPH model rats and BPH patients

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