The Gerontology Research Center of Jianghan University, The Sixth Hospital of Wuhan (Affiliated Hospital of Jianghan University), Jianghan University, Wuhan, China; Wuhan Institute of Biomedical Sciences, School of Medical, Jianghan University, Wuhan, China.
The Gerontology Research Center of Jianghan University, The Sixth Hospital of Wuhan (Affiliated Hospital of Jianghan University), Jianghan University, Wuhan, China.
Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
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, co-expression 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.
良性前列腺增生症（BPH）是一种与年龄相关的男性疾病。间质/基质细胞和上皮细胞的相互作用对前列腺功能至关重要。在这项研究中，人非恶性前列腺上皮 RWPE-1 细胞与经睾丸酮（TE）暴露的前列腺基质成纤维细胞 WPMY-1 细胞（TE-WPMY-1）共培养。观察 RWPE-1 的存活率、上皮-间质转化（EMT）和胶原沉积。通过高通量 RNA 测序探索 WPMY-1 衍生的外泌体样小泡（WPMY-1-exo）中 circRNAs、lncRNAs 和 mRNAs 的表达谱。首先，TE-WPMY-1 和 TE-WPMY-1-exo 均显著促进 RWPE-1 细胞增殖。其次，TE-WPMY-1-exo 与对照组之间有 41 个 circRNAs、132 个 lncRNAs 和 1057 个 mRNAs 差异表达（DE）。功能富集分析、共表达分析和定量实时 PCR 验证表明，差异表达的 RNA 在细胞增殖、结构、表型和纤维化中发挥重要作用。最后，用 GW4869 阻断 WPMY-1-exo 的生物发生/释放可减弱 TE-WPMY-1 刺激的 RWPE-1 细胞 EMT 和胶原沉积。总之，我们的研究结果表明，WPMY-1-exo 调节前列腺上皮细胞的表型变化和胶原沉积。为理解 BPH 中 WPMY-1 诱导的 RWPE-1 细胞 EMT 和纤维化的潜在机制提供了新的依据。
