Proliferative mechanism of benign prostatic hyperplasia by NLRP3 inflammasome through the complement pathway

• Published in: International journal of urology 2024-12, Vol.31 (12), p.1429-1437
• Main Authors: Hata, Junya, Matsuoka, Kanako, Harigane, Yuki, Yaginuma, Kei, Akaihata, Hidenori, Meguro, Satoru, Honda‐Takinami, Ruriko, Onagi, Akifumi, Sato, Yuichi, Ogawa, Soichiro, Uemura, Motohide, Kojima, Yoshiyuki
• Format: Article
• Language: English
• Subjects: Animals; benign prostatic hyperplasia; Caspase; Caspase 1 - metabolism; Cell Proliferation - drug effects; Complement activation; Complement component C5a; complement pathway; Disease Models, Animal; Hyperplasia; Inflammasomes; Inflammasomes - metabolism; Interleukin-18 - blood; Interleukin-18 - metabolism; Interleukin-1beta - blood; Interleukin-1beta - metabolism; Male; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Polymerase chain reaction; Prostate; Prostate - immunology; Prostate - metabolism; Prostate - pathology; Prostatic Hyperplasia - drug therapy; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Rats; Rats, Sprague-Dawley; Resveratrol; Resveratrol - pharmacology; Therapeutic targets; Western blotting
• ISSN: 0919-8172; 1442-2042; 1442-2042
• DOI: 10.1111/iju.15576

Objectives The expressions of complement component C5a and NLRP3 inflammasome and the antiproliferative effect of resveratrol in benign prostatic hyperplasia (BPH) model rat were analyzed to clarify the BPH proliferative mechanism. Methods This study used the pathological stromal‐dominant BPH model rat by urogenital sinus implantation (UGS). Expression of C5a, NLRP3, Caspase‐1, IL‐1β, and IL‐18 using rat BPH tissues at 2, 3, and 8 weeks (n = 6, respectively) after UGS implantation were analyzed by qRT‐PCR, western blotting analysis, and immunohistochemical (IHC) analysis. Serum IL‐1β levels in BPH model and sham rats were measured by enzyme‐linked immunosorbent assay. Furthermore, resveratrol, as the NLRP3 pathway inhibitor, was administered to BPH model rat to assess the antiproliferative effect on the BPH proliferative process. The proliferative effect on prostate was evaluated by Ki‐67 protein expression. Results The expression levels of C5a, NLRP3, Caspase‐1, IL‐1β, and IL‐18 in qRT‐PCR, western blotting, and IHC were significantly upregulated in BPH tissues compared to control prostate tissues and showed increases with time (all p