LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia.
LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia.
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DOI：
10.1038/srep27051
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发表时间：
2016-05-31
影响因子：
4.6
通讯作者：
Wang L
中科院分区：
文献类型：
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作者：
He Y;Ou Z;Chen X;Zu X;Liu L;Li Y;Cao Z;Chen M;Chen Z;Chen H;Qi L;Wang L
令人信服的证据表明，良性前列腺增生（BPH）的发展涉及上皮-间质转化（EMT）过程中源自前列腺上皮的间质样细胞的积累。转化生长因子(TGF)-β在前列腺上皮细胞中诱导低E-cadherin和高vimentin表达的EMT表型。在这里，我们报道LPS/TLR4信号传导诱导骨形态发生蛋白和激活素膜结合抑制剂（BAMBI）的下调，从而增强前列腺增生过程中EMT过程中的TGF-β信号传导。此外，我们发现炎症的BPH组织的TLR4平均染色评分明显高于无炎症的BPH组织（分别为5.13±1.21和2.96±0.73,P < 0.001）。炎症浸润患者的年龄（P = 0.020）、BMI （P = 0.026）、前列腺体积（P = 0.024）、总IPSS评分（P = 0.009）和IPSS- s （P < 0.001）较高。Pearson相关系数及多元回归分析显示，炎症组TLR4 mRNA表达水平与年龄、BMI、血清PSA水平、IPSS急症、夜尿症亚评分呈显著正相关。这些发现为TLR4扩增的EMT过程以及TLR4水平与储存LUTS之间的关系提供了新的见解，表明慢性炎症对BPH的发病机制至关重要。
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.