Di-n-butyl phthalate induces NF-κB-mediated senescence-associated secretory phenotype to promote epithelial proliferation, epithelial-mesenchymal transition, and benign prostatic hyperplasia through IL-8/CXCR2 signaling.
Key Findings
Results
DBP exposure promoted benign prostatic hyperplasia in a Sprague-Dawley rat model.
A DBP-exposed SD rat model was established to confirm the promoting effect of DBP on BPH.
Both in vivo and in vitro studies confirmed that inhibition of CXCR2 reverses the promoting effect of DBP exposure on BPH.
The rat model served as the primary in vivo system for validating mechanistic findings from cell culture experiments.
Results
DBP exposure promoted cellular senescence in BPH-1 cells, as evidenced by secretion of senescence-associated secretory phenotype (SASP)-related factors.
Transcriptome sequencing analysis of BPH-1 cells after DBP exposure revealed that DBP promotes cellular senescence.
The senescence was characterized by the secretion of SASP-related factors.
The NF-κB pathway was identified as mediating DBP-induced SASP.
Results
DBP-induced SASP primarily promotes cell proliferation and epithelial-mesenchymal transition (EMT) through the release of IL-8.
Co-culture of DBP-exposed cells with unexposed BPH-1 cells showed that DBP-induced SASP promotes cell proliferation and EMT.
IL-8 was identified as the primary SASP factor responsible for these effects.
IL-8 exerts its effects by binding to CXCR2 receptor on unexposed cells.
Results
Inhibition of CXCR2 reversed the promoting effects of DBP exposure on BPH both in vivo and in vitro.
Both in vivo and in vitro studies confirmed that CXCR2 inhibition reverses DBP's promotion of BPH.
This finding validates the IL-8/CXCR2 axis as a key mechanistic pathway linking DBP exposure to BPH progression.
CXCR2 inhibition reversed effects on both epithelial proliferation and EMT.
Background
DBP, a prevalent environmental endocrine disruptor, is associated with various genitourinary diseases including BPH.
DBP is described as a 'prevalent environmental endocrine disruptor.'
The study establishes a mechanistic link between DBP exposure and BPH progression.
These findings provide 'new insights into the mechanisms by which DBP exposure contributes to BPH progression.'
Li T, Zhang Y, Zhou X, Ji S, Zhou Z, Wang W, et al.. (2026). Di-n-butyl phthalate induces NF-κB-mediated senescence-associated secretory phenotype to promote epithelial proliferation, epithelial-mesenchymal transition, and benign prostatic hyperplasia.. Environment international. https://doi.org/10.1016/j.envint.2026.110085