Di-n-butyl phthalate induces NF-κB-mediated senescence-associated secretory phenotype to promote epithelial proliferation, epithelial-mesenchymal transition, and benign prostatic hyperplasia

Di-n-butyl phthalate (DBP), a prevalent environmental endocrine disruptor, is associated with various genitourinary diseases. In this study, a DBP-exposed Sprague-Dawley (SD) rat model was established to confirm the promoting effect of DBP on benign prostatic hyperplasia (BPH). Transcriptome sequencing analysis of BPH-1 cells after DBP exposure revealed that DBP promotes cellular senescence, as evidenced by the secretion of senescence-associated secretory phenotype (SASP)-related factors. Co-culture of DBP-exposed cells with unexposed BPH-1 cells showed that DBP-induced SASP primarily promotes cell proliferation and epithelial-mesenchymal transition (EMT) through the release of IL-8, which binds to CXCR2. Furthermore, both in vivo and in vitro studies confirmed that inhibition of CXCR2 reverses the promoting effect of DBP exposure on BPH. These findings provide new insights into the mechanisms by which DBP exposure contributes to BPH progression.