The Expression of Inflammatory Mediators in Bladder Pain Syndrome.
The Expression of Inflammatory Mediators in Bladder Pain Syndrome.
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DOI：
10.1016/j.eururo.2016.02.058
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发表时间：
2016-08
期刊：
影响因子：
23.4
通讯作者：
McMahon SB
中科院分区：
文献类型：
--
作者：
Offiah I;Didangelos A;Dawes J;Cartwright R;Khullar V;Bradbury EJ;O'Sullivan S;Williams D;Chessell IP;Pallas K;Graham G;O'Reilly BA;McMahon SB
膀胱疼痛综合征（BPS）的病理学知之甚少。治疗策略是经验性的，疗效有限，受影响的患者生活质量下降。我们研究了膀胱内炎症介质导致BPS病理的假设。从2011年10月至2012年10月，从科克大学妇产医院招募了15名BPS女性和15名无膀胱疼痛的压力性尿失禁女性。在膀胱镜检查过程中，取5 mm膀胱活检组织并进行基因表达分析。在实验室动物中测试了所鉴定的基因的效果。我们研究了96个炎症相关基因在患病和健康膀胱中的表达。我们使用Pearson相关系数测量基因和患者临床特征之间的相关性。分析显示15个差异表达基因，在复制研究中得到证实。FGF 7和CCL 21与临床结果显著相关。大鼠膀胱灌注CCL 21可引起膀胱兴奋性增加和脊髓神经元c-fos活性增加。CCL 21非典型受体敲除小鼠在用CCL 21刺激膀胱时比野生型同窝出生的小鼠显示出显著更多的c-fos。接受FGF 7治疗的动物没有变化。患者样本的变异性是主要限制。我们使用主成分分析来识别患者组内的相似性。我们的研究在BPS中鉴定了两种生物学相关的炎症介质，并证明了CCL 21的伤害性信号传导增加。操纵这种配体是一种潜在的治疗BPS的新策略。我们比较了膀胱疼痛综合征（BPS）患者和无疼痛的对照组膀胱活检组织中的基因表达，并确定了两个在BPS患者中增加并与临床特征相关的基因。我们在实验室动物中测试了这些基因的影响，证实了它们在膀胱疼痛中的作用。在BPS中操纵这些基因是一种潜在的治疗策略。膀胱疼痛综合征（BPS）的病理学仍然知之甚少，其治疗是困难的。我们确定了介质，从我们的研究他们的行动在膀胱的实验室动物，可能涉及疾病的病理。这些介质是BPS治疗的未开发的治疗靶点。
Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy. Bladder pain syndrome (BPS) pathology remains poorly understood, and its treatment is difficult. We identified mediators that, from our study of their action in the bladders of laboratory animals, may be implicated in disease pathology. These mediators are unexploited therapeutic targets for BPS treatment.