期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 411, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2020.115384
关键词
Benign prostatic hyperplasia; Stromal cells; Epithelial cells; Exosome-like vesicles; Epithelial-mesenchymal transition
资金
- State Natural Sciences Fund of China [81703594, 81603177]
The study highlighted the impact of prostatic stromal cell-derived exosomes on the phenotype changes and collagen deposition of prostate epithelial cells, providing insights into a potential mechanism in benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is an age-related disease in men. Mesenchymal /stromal and epithelial cells interactions are essential to prostate functions. In this study, human nonmalignant prostate epithelial RWPE-1 cells were cocultured with testosterone (TE) -exposed prostate stromal fibroblasts WPMY-1 cells (TE-WPMY-1). The survival rate, epithelial-mesenchymal transition (EMT) and collagen deposition of RWPE-1 were observed. The expression profiles of circRNAs, lncRNAs and mRNAs in WPMY-1-derived exosome-like vesicles (WPMY-1-exo) were explored by high-throughput RNA sequencing. Firstly, both TE-WPMY-1 and TE-WPMY-1-exo significantly promoted RWPE-1 cells proliferation. Secondly, 41 circRNAs, 132 lncRNAs and 1057 mRNAs were differentially expressed (DE) between TE-WPMY-1-exo and the control. Functional enrichment analyses, coexpression analyses and quantitative real-time PCR verification showed that the DE RNAs played important roles in cell proliferation, structure, phenotype and fibrosis. Lastly, blocking WPMY-1-exo biogenesis/release by GW4869 can attenuate TE-WPMY-1-stimulated RWPE-1 cells EMT and collagen deposition. Taken together, our results indicated that WPMY-1-exo modulated the phenotypes changes and collagen deposition of prostate epithelial cells. It provided a novel basis for understanding the underlying mechanisms of RWPE-1 cells EMT and fibrosis induced by WPMY-1 in BPH.
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