The Role of PIEZO1 in Urinary Bladder Function and Dysfunction in a Rodent Model of Cyclophosphamide-Induced Cystitis.
The Role of PIEZO1 in Urinary Bladder Function and Dysfunction in a Rodent Model of Cyclophosphamide-Induced Cystitis.
复制标题
DOI：
10.3389/fpain.2021.748385
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Vizzard MA
中科院分区：
文献类型：
--
作者：
Beča KIK;Girard BM;Heppner TJ;Hennig GW;Herrera GM;Nelson MT;Vizzard MA
在尿膀胱中，机械敏感的离子通道（MSC）是膀胱伸展到接力PN和CNS的感觉信号的转移研究表明，压电是通过机械拉伸或药物激动剂通过Yoda1激活的。建议我们在临床膀胱病理学中发挥作用在给药后长达16个小时，与环磷酰胺（CYP）模型相比，我们发现几种候选MSC的基因表达（TRPV1，TRPV4，Piezo1和Piezo2）在尿液中都进行了更新，在慢性CYP诱发的膀胱炎之后，尿液中均未使用该模型，但急性CYP诱导的膀胱炎。通过Yoda1在急性和中间CYP处理中激活，但在幼稚（无CYP）或慢性CYP处理中进行激活。压电可能通过在包括claudin-1，claudin-8和zona occludens-1的尿液中的几个紧密连接基因的下调来导致病理膀胱功能障碍。成为治疗IC/BP等病理治疗的未来，临床目标。
In the urinary bladder, mechanosensitive ion channels (MSCs) underlie the transduction of bladder stretch into sensory signals that are relayed to the PNS and CNS. PIEZO1 is a recently identified MSC that is Ca2+ permeable and is widely expressed throughout the lower urinary tract. Recent research indicates that PIEZO1 is activated by mechanical stretch or by pharmacological agonism via Yoda1. Aberrant activation of PIEZO1 has been suggested to play a role in clinical bladder pathologies like partial bladder outlet obstruction and interstitial cystitis/bladder pain syndrome (IC/BPS). In the present study, we show that intravesical instillation of Yoda1 in female Wistar rats leads to increased voiding frequency for up to 16 hours after administration compared to vehicle treatment. In a cyclophosphamide (CYP) model of cystitis, we found that the gene expression of several candidate MSCs (Trpv1, Trpv4, Piezo1, and Piezo2) were all upregulated in the urothelium and detrusor following chronic CYP-induced cystitis, but not acute CYP-induced cystitis. Functionally with this model, we show that Ca2+ activity is increased in urothelial cells following PIEZO1 activation via Yoda1 in acute and intermediate CYP treatment, but not in naïve (no CYP) nor chronic CYP treatment. Lastly, we show that activation of PIEZO1 may contribute to pathological bladder dysfunction through the downregulation of several tight junction genes in the urothelium including claudin-1, claudin-8, and zona occludens-1. Together, these data suggest that PIEZO1 activation plays a role in dysfunctional voiding behavior and may be a future, clinical target for the treatment of pathologies like IC/BPS.
登录
查看更多内容
影响因子：
12.8
作者：
Liu Q;Sun B;Zhao J;Wang Q;An F;Hu X;Yang Z;Xu J;Tan M;Li L
通讯作者：
Li L
DOI：
10.1016/j.juro.2011.03.132
发表时间：
2011-08
期刊：
The Journal of urology
影响因子：
--
作者：
Berry SH;Elliott MN;Suttorp M;Bogart LM;Stoto MA;Eggers P;Nyberg L;Clemens JQ
通讯作者：
Clemens JQ
DOI：
10.1152/ajprenal.00282.2013
发表时间：
2013-10-01
影响因子：
4.2
作者：
Carattino, Marcelo D.;Prakasam, H. Sandeep;Apodaca, Gerard
通讯作者：
Apodaca, Gerard
DOI：
10.1073/pnas.1005333107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Everaerts, Wouter;Zhen, Xiaoguang;Voets, Thomas
通讯作者：
Voets, Thomas
DOI：
10.1152/ajprenal.90718.2008
发表时间：
2009-04-01
影响因子：
4.2
作者：
Kullmann, F. Aura;Shah, M. A.;de Groat, W. C.
通讯作者：
de Groat, W. C.