Upregulation of osteopontin expression in prostatic stromal cells via the interaction with prostatic epithelial cells contribute to inflammation-related prostatic fibrosis

OBJECTIVE: This study aimed to investigate the role of osteopontin (OPN) in promoting prostatic fibrosis through inflammation. METHODS: OPN expression in the prostates of BPH patients was detected using immunohistochemistry, and its correlation with inflammatory grade, preoperative IPSS, and the percentage of collagen fiber was evaluated, respectively. RNA sequencing (RNA-Seq) identified differentially expressed genes (DEGs) in Spp1-OE WPMY-1 cells. A non-contact co-culture system of BPH-1 and WPMY-1 cells (with or without rhOPN treatment), Spp1-shRNA, or Spp1-OE WPMY-1 cells was established to assess WPMY-1 cells mRNA expression of PTGS2, CXCL1, CCL2, and Spp1 by RT-PCR. RESULTS: The expression of OPN in prostate stromal cells was significantly higher in the symptomatic BPH (S-BPH) group, the IPSS 20-35 (severe symptom) group, and the Moderate + Severe inflammation group compared to the asymptomatic BPH (A-BPH) group, the IPSS 8-19 (moderate symptom) group, and the No + Mild inflammation group. Furthermore, OPN expression was positively correlated with preoperative IPSS and the percentage of collagen fibers in S-BPH patients. RNA-Seq identified some DEGs between Vector and Spp1-OE WPMY-1 cells, which are closely related to inflammation and fibrosis. In vitro experiments demonstrated that the expression of PTGS2, CXCL1, CCL2, and Spp1 significantly increased in WPMY-1 cells co-cultured with BPH-1 cells, particularly following treatment with rhOPN. Spp1-shRNA WPMY-1 cells co-cultured with BPH-1 cells exhibited reduced expression of PTGS2, CXCL1, and CCL2, whereas Spp1-OE WPMY-1 cells co-cultured with BPH-1 cells showed an increased expression of these genes. CONCLUSIONS: OPN may be involved in the occurrence of prostatic inflammation and fibrosis. The upregulation of OPN expression in prostatic stromal cells may contribute to prostatic fibrosis by interacting with prostatic epithelial cells to exacerbate inflammatory processes.