title: LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia.
abstract: 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.
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xiongbing
authors.initials: X
authors.lastname: Zu
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecologic Oncology, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Minfeng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Hequn
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007610:Kallikreins / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020728:Transurethral Resection of Prostate
chemical_list: C485671:BAMBI protein, human; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen