Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis.
Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis.
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DOI：
10.1371/journal.pone.0104216
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ogawa O
中科院分区：
文献类型：
--
作者：
Okinami T;Imamura M;Nishikawa N;Negoro H;Sugino Y;Yoshimura K;Kanematsu A;Hashitani H;Ogawa O
下尿路症状（LUTS）包括储尿、排尿和排尿后症状，是许多泌尿系统疾病的特征。储尿症状是这些症状中最常见的，并且与膀胱过度活动症和非细菌性膀胱炎症如间质性膀胱炎/膀胱疼痛综合征（IC/BPS）相关。缝隙连接是膀胱过度活动状态的关键调节因子，据报道与病理性膀胱炎症有关。在这里，我们报告参与间隙连接的病因学储存症状的膀胱炎症。在这项研究中，环磷酰胺诱导的膀胱炎被改编为膀胱炎症模型。环磷酰胺处理的小鼠表现出典型的储存症状，包括排尿频率增加和膀胱容量减少，同时上调连接蛋白43（GJA 1），膀胱中的主要间隙连接蛋白之一。在等长收缩实验中，治疗组小鼠膀胱平滑肌条的自发收缩较对照组明显，这种收缩可被间隙连接抑制剂甘珀酸减弱。在排尿行为研究中，另一种间隙连接抑制剂18α-大黄酸可减轻治疗小鼠的储尿症状，其特征为频繁排尿。这些结果表明，环磷酰胺诱导的膀胱炎小鼠模型显示出与膀胱炎症相关的临床储存症状，并且膀胱中的间隙连接可能是这些储存症状的关键分子。因此，膀胱间隙连接可能是膀胱炎症中储存症状的替代治疗靶点。
Lower urinary tract symptoms (LUTS) include storage, voiding and post-micturition symptoms, featuring many urological diseases. Storage symptoms are the most frequent among these and associated with overactive bladder and non-bacterial bladder inflammation such as interstitial cystitis/bladder pain syndrome (IC/BPS). Gap junction, a key regulator of hyperactive conditions in the bladder, has been reported to be involved in pathological bladder inflammation. Here we report involvement of gap junction in the etiology of storage symptoms in bladder inflammation. In this study, cyclophosphamide-induced cystitis was adapted as a model of bladder inflammation. Cyclophosphamide-treated mice showed typical storage symptoms including increased urinary frequency and reduced bladder capacity, with concurrent up-regulation of connexin 43 (GJA1), one of the major gap junction proteins in the bladder. In isometric tension study, bladder smooth muscle strips taken from the treated mice showed more pronounced spontaneous contraction than controls, which was attenuated by carbenoxolone, a gap junction inhibitor. In voiding behavior studies, the storage symptoms in the treated mice characterized by frequent voiding were alleviated by 18α-glycyrrhetinic acid, another gap junction inhibitor. These results demonstrate that cyclophosphamide-induced mouse model of cystitis shows clinical storage symptoms related with bladder inflammation and that gap junction in the bladder may be a key molecule of these storage symptoms. Therefore, gap junction in the bladder might be an alternative therapeutic target for storage symptoms in bladder inflammation.
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DOI：
10.1002/ar.a.20108
发表时间：
2004-10-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Efimov, IR;Nikolski, VP;Boyett, M
通讯作者：
Boyett, M
影响因子：
6.6
作者：
Johnson, Michael H.;Nepple, Kenneth G.;Kibel, Adam S.
通讯作者：
Kibel, Adam S.
影响因子：
5.6
作者：
Imamura M;Sugino Y;Long X;Slivano OJ;Nishikawa N;Yoshimura N;Miano JM
通讯作者：
Miano JM
影响因子：
23.4
作者：
Irwin, Debra E.;Milsom, Ian;Abrams, Paul
通讯作者：
Abrams, Paul
影响因子：
3.7
作者：
Heinrich M;Oberbach A;Schlichting N;Stolzenburg JU;Neuhaus J
通讯作者：
Neuhaus J