Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice.
Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice.
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环磷酰胺诱导的间质 Cajal 样细胞中 HCN1 通道上调导致小鼠膀胱过度活跃
DOI：
10.1038/emm.2017.31
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发表时间：
2017-04-21
影响因子：
12.8
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Liu Q;Long Z;Dong X;Zhang T;Zhao J;Sun B;Zhu J;Li J;Wang Q;Yang Z;Hu X;Li L
超极化激活的环核苷酸门控（HCN）通道被证实在膀胱间质Cajal样细胞（ICC-LC）中表达，但关于其在膀胱炎相关膀胱功能障碍中的可能作用知之甚少。本研究旨在确定HCN通道在炎症条件下调节膀胱功能的功能作用。将60只雌性野生型C57 BL/6 J小鼠和60只雌性HCN 1基因敲除小鼠分别随机分配到实验组和对照组。成功建立了环磷酰胺（Cyclophosphamide，CTX）诱导的小鼠膀胱炎模型。HCN处理显著增强HCN通道蛋白表达和I h密度，并显著改变膀胱HCN 1通道调节蛋白。卡巴胆碱（CCH）和福司可林（FSK）对CYP处理的野生型（WT）小鼠膀胱ICC-LC [Ca 2+] i有显著影响，HCN 1通道阻断可显著降低CCH和FSK对未处理和CYP处理小鼠膀胱ICC-LC [Ca 2+] i的影响。HCN 1处理可显著增强逼尿肌条的自发收缩和CCH（0.001-10 μ M）诱导的时相收缩，而HCN 1通道缺失可显著减弱这种作用。最后，我们证明CYP诱导的膀胱过度活动在HCN 1 −/−小鼠中发生逆转。综上所述，我们的研究结果表明，CYP诱导的增强HCN 1通道的表达和功能在膀胱ICC-LC是必不可少的膀胱炎相关的膀胱过度活动的发展，表明HCN 1通道可能是一个新的治疗目标，用于管理膀胱过度活动。
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively. Cyclophosphamide (CYP)-induced cystitis models were successfully established in these mice. CYP treatment significantly enhanced HCN channel protein expression and I h density and significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH) and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca 2+] i in CYP-treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased the effects of CCH and FSK on bladder ICC-LC [Ca 2+] i in both naive and CYP-treated mice. CYP treatment significantly potentiated the spontaneous contractions and CCH (0.001–10 μ M)-induced phasic contractions of detrusor strips, and HCN1 channel deletion significantly abated such effects. Finally, we demonstrated that the development of CYP-induced bladder overactivity was reversed in HCN1−/− mice. Taken together, our results suggest that CYP-induced enhancements of HCN1 channel expression and function in bladder ICC-LCs are essential for cystitis-associated bladder hyperactivity development, indicating that the HCN1 channel may be a novel therapeutic target for managing bladder hyperactivity.
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影响因子：
5.6
作者：
Freitas, Raquel D. S.;Costa, Kesiane M.;Campos, Maria M.
通讯作者：
Campos, Maria M.
DOI：
10.1016/j.juro.2009.02.108
发表时间：
2009-07
期刊：
The Journal of urology
影响因子：
--
作者：
Anderson UA;Carson C;McCloskey KD
通讯作者：
McCloskey KD
影响因子：
23.4
作者：
Humphrey, Louise;Arbuckle, Rob;Abraham, Lucy
通讯作者：
Abraham, Lucy
影响因子：
6.6
作者：
Nasrin, Sweety;Masuda, Eiji;Yamada, Shizuo
通讯作者：
Yamada, Shizuo
大鼠膀胱中超极化激活的环核苷酸门控通道及其亚型的鉴定
影响因子：
2.1
作者：
He, Peng;Deng, Jianping;Li, Longkun
通讯作者：
Li, Longkun