Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, PR China.
Department of Urology, First Affiliated Hospital of Medical College of Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Region, PR China.
Biochem Biophys Res Commun. 2018 Sep 5;503(2):420-427. doi: 10.1016/j.bbrc.2018.04.050. Epub 2018 Jun 29.
In a previous work using guinea pig prostate, we have identified a novel interstitial cells of Cajal (ICCs) which possess close contacts between sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs in mediating excitatory neural inputs was therefore studied using isolated murine prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and Western blotting analyses revealed that prostatic ICCs under a quiescent state expressed abundantly the rate-limiting enzymes essential for catecholamine synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1β, IL-8, ICAM-1 and TNF-α) could significantly stimulate the expression levels of the rate-limiting enzymes of catecholamine production in prostate ICCs. Mechanistically, the above-mentioned stimulatory effects of proinflammatory cytokines appeared to be mediated via activation of NF-κB, HIF-1α and HDACs signaling pathways. Considering that prostatic catecholamine overactivity serves as an essential etiology of pelvic pain by indirectly stimulating the smooth muscle cell proliferation, or by directly causing muscular spasm, our results collectively suggest that targeting the NF-κB, HIF-1α and HDACs pathways in prostate ICCs be considered as a new strategy for treatment of chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall, the current study should shed novel light on the biology of this unique prostate ICCs.
在之前使用豚鼠前列腺的研究中，我们鉴定了一种新型的 Cajal 间质细胞（ICCs），其与平滑肌细胞之间存在密切接触。因此，我们通过胶原酶消化结合 FACS 方法，研究了分离的小鼠前列腺 ICCs 中介导兴奋性神经输入的能力。RT-PCR 和 Western blot 分析表明，在静止状态下，前列腺 ICCs 大量表达儿茶酚胺合成所必需的限速酶。此外，不同的促炎细胞因子（如 IL-1β、IL-8、ICAM-1 和 TNF-α）可显著刺激前列腺 ICCs 中儿茶酚胺产生的限速酶的表达水平。在机制上，上述促炎细胞因子的刺激作用似乎是通过 NF-κB、HIF-1α 和 HDACs 信号通路的激活来介导的。考虑到前列腺儿茶酚胺过度活跃通过间接刺激平滑肌细胞增殖，或直接引起肌肉痉挛，是慢性前列腺炎（CP）相关慢性骨盆疼痛综合征（CPPS）的重要病因，我们的研究结果表明，针对前列腺 ICCs 中的 NF-κB、HIF-1α 和 HDACs 途径可能是治疗 CPPS 的新策略。总的来说，本研究应该为这种独特的前列腺 ICCs 的生物学提供新的见解。
