Heat injured stromal cells‐derived exosomal EGFR enhances prostatic wound healing after thulium laser resection through EMT and NF‐κB signaling

作者：Fei Shi, Zheng Deng, Zheng Zhou, Bo Jiang, Chenyi Jiang, Ruizhe Zhao, Feng Sun, Di Cui, Meng‐Hao Sun, Qian Sun, Xing‐Jie Wang, Qi Wu, Shujie Xia, Bang-Min Han · 发表于：The Prostate · 年份：2019 · DOI：10.1002/pros.23827 · 被引用次数：16 · 研究领域：Urinary Bladder and Prostate Research、Extracellular vesicles in disease、Prostate Cancer Diagnosis and Treatment

BACKGROUND: This study investigated shallow heat injury to prostate stromal fibroblasts and epithelial cells and their interaction to regulate the wound healing and the underlying molecular events. METHODS: Prostate stromal fibroblasts and epithelial cells were cultured individually or cocultured and subjected to shallow heat injury for assessments of cell proliferation, migration, apoptosis, cell cycle distribution, and gene expression. The supernatant of heat-injured WPMY-1 cells was collected for exosome extraction and assessments. Furthermore, beagle dogs received thulium laser resection of the prostate (TmLRP) and randomly divided into Gefitinib, GW4869, and control treatment for the histological analysis, tissue re-epithelialization, and epidermal growth factor receptor (EGFR) expression on the prostatic wound surface. Immunofluorescence was to evaluate p63-positive basal progenitor cell trans-differentiation and macrophage polarization and ELISA was to detect cytokine levels in beagles' urine. RESULTS: Shallow heat injury caused these cells to enter a stressed state and enhanced their crosstalk. The prostate stromal fibroblasts produced and secreted more exosomal-EGFR and other cytokines and chemokines after shallow heat injury, resulting in increased proliferation and migration of prostate epithelial cells during wound healing. The wound healing of the canine prostatic urethra following the TmLRP procedure was slower in the Gefitinib and GW4869 treatment group than in...