Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Molecular and Environmental Toxicology Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Prostate. 2014 Apr;74(4):346-58. doi: 10.1002/pros.22751. Epub 2013 Nov 30.
Prostatic inflammation is an important factor in development and progression of BPH/LUTS. This study was performed to characterize the normal development and vascular anatomy of the mouse prostate and then examine, for the first time, the effects of prostatic inflammation on the prostate vasculature.
Adult mice were perfused with India ink to visualize the prostatic vascular anatomy. Immunostaining was performed on the E16.5 UGS and the P5, P20, and adult prostate to characterize vascular development. Uropathogenic E. coli 1677 was instilled transurethrally into adult male mice to induce prostate inflammation. RT-PCR and BrdU labeling was performed to assay anigogenic factor expression and endothelial proliferation, respectively.
An artery on the ventral surface of the bladder trifurcates near the bladder neck to supply the prostate lobes and seminal vesicle. Development of the prostatic vascular system is associated with endothelial proliferation and robust expression of pro-angiogenic factors Pecam1, Tie1, Tek, Angpt1, Angpt2, Fgf2, Vegfa, Vegfc, and Figf. Bacterial-induced prostatic inflammation induced endothelial cell proliferation and increased vascular density but surprisingly decreased pro-angiogenic factor expression.
The striking decrease in pro-angiogenic factor mRNA expression associated with endothelial proliferation and increased vascular density during inflammation suggests that endothelial response to injury is not a recapitulation of normal development and may be initiated and regulated by different regulatory mechanisms.
前列腺炎症是 BPH/LUTS 发展和进展的一个重要因素。本研究旨在描述小鼠前列腺的正常发育和血管解剖结构,然后首次研究前列腺炎症对前列腺血管系统的影响。
成年小鼠用印度墨汁灌注以显示前列腺的血管解剖结构。对 E16.5 UGS 和 P5、P20 和成年前列腺进行免疫染色,以描述血管发育。将尿路致病性大肠杆菌 1677 经尿道灌注到成年雄性小鼠中以诱导前列腺炎症。进行 RT-PCR 和 BrdU 标记以分别检测血管生成因子的表达和内皮细胞增殖。
膀胱腹侧面的一条动脉在膀胱颈部附近分为三支,供应前列腺叶和精囊。前列腺血管系统的发育与内皮细胞增殖和促血管生成因子 Pecam1、Tie1、Tek、Angpt1、Angpt2、Fgf2、Vegfa、Vegfc 和 Figf 的强烈表达相关。细菌诱导的前列腺炎症诱导内皮细胞增殖和增加血管密度,但令人惊讶的是,促血管生成因子的表达减少。
炎症过程中内皮细胞增殖和血管密度增加伴随着促血管生成因子 mRNA 表达的显著下降,这表明内皮对损伤的反应不是正常发育的再现,可能由不同的调节机制引发和调节。