Compelling evidence suggests that benign prostatic hyperplasia (BPH) development involves accumulation of mesenchymal-like cells derived from the prostatic epithelium by epithelial-mesenchymal transition (EMT). Transforming growth factor (TGF)-β induces EMT phenotypes with low E-cadherin and high vimentin expression in prostatic epithelial cells. Here we report that LPS/TLR4 signalling induces down-regulation of the bone morphogenic protein and activin membrane-bound inhibitor (BAMBI), which enhances TGF-β signalling in the EMT process during prostatic hyperplasia. Additionally, we found that the mean TLR4 staining score was significantly higher in BPH tissues with inflammation compared with BPH tissues without inflammation (5.13 ± 1.21 and 2.96 ± 0.73, respectively; P < 0.001). Moreover, patients with inflammatory infiltrate were more likely to have a higher age (P = 0.020), BMI (P = 0.026), prostate volume (P = 0.024), total IPSS score (P = 0.009) and IPSS-S (P < 0.001). Pearson's correlation coefficient and multiple regression analyses demonstrated that TLR4 mRNA expression level was significantly positively associated with age, BMI, serum PSA levels, urgency and nocturia subscores of IPSS in the inflammatory group. These findings provide new insights into the TLR4-amplified EMT process and the association between TLR4 levels and storage LUTS, suggesting chronic inflammation as vital to the pathogenesis of BPH.
Scientific reports. 2016 May 31*** epublish ***
Yao He, Zhenyu Ou, Xiang Chen, Xiongbing Zu, Longfei Liu, Yuan Li, Zhenzhen Cao, Minfeng Chen, Zhi Chen, Hequn Chen, Lin Qi, Long Wang
Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Gynecologic Oncology, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.