Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis.
Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis.
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DOI：
10.1038/s12276-018-0088-z
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发表时间：
2018-05-07
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;Sun B;Zhao J;Wang Q;An F;Hu X;Yang Z;Xu J;Tan M;Li L
压电通道是一种机械转移的介体，而在几种临床上，压电性异常与膀胱炎相关的膀胱功能障碍的作用已与cy症的一百个cy症（cycloply）cy cy cysipsightion相关。 ed到控件， CYP-4H，CYP-48H和CYP-8D组成功地诱导了这些大鼠的急性或慢性膀胱炎。 TX4）显着减弱了膀胱多动症CYP-8D通过抑制膀胱ICC-LC中的压电通道。模式Na+/Ca2+交换器1（NCX1）在CYP-8D大鼠的膀胱ICC-LC中，我们认为Piezo1通道在CYP诱导的慢性膀胱炎中的功能作用是基于其与NCX1的协同作用，这可能会显着增强CA2+ ICC的blads and ca2+ iCC。慢性的新型治疗靶标膀胱炎相关的膀胱多动症。
控制离子通过细胞膜的蛋白质在间隙膀胱炎/疼痛的膀胱综合征中暗示（IC/PBS）。美国，该膜通道蛋白的作用称为Piezo1。患有患者IC/PBS。
The Piezo1 channel is a mechanotransduction mediator, and Piezo1 abnormalities have been linked to several clinical disorders. However, the role of the Piezo1 channel in cystitis-associated bladder dysfunction has not been documented. The current study aimed to discover the functional role of this channel in regulating bladder activity during cyclophosphamide (CYP)-induced cystitis. One hundred four female rats were randomly assigned to the control, CYP-4h, CYP-48h and CYP-8d groups. CYP successfully induced acute or chronic cystitis in these rats. CYP treatment for 48h or 8d significantly increased Piezo1 channel expression in bladder interstitial Cajal-like cells (ICC-LCs), and the increase in CYP-8d rats was more prominent. In addition, 2.5 μM Grammostola spatulata mechanotoxin 4 (GsMTx4) significantly attenuated bladder hyperactivity in CYP-8d rats by inhibiting the Piezo1 channel in bladder ICC-LCs. Furthermore, by using GsMTx4 and siRNA targeting the Piezo1 channel, we demonstrated that hypotonic stress-induced Piezo1 channel activation significantly triggered Ca2+ and Na+ influx into bladder ICC-LCs during CYP-induced chronic cystitis. In addition, the Piezo1 channel functionally interacted with the relatively activated reverse mode of Na+/Ca2+ exchanger 1 (NCX1) in bladder ICC-LCs from CYP-8d rats. In conclusion, we suggest that the functional role of the Piezo1 channel in CYP-induced chronic cystitis is based on its synergistic effects with NCX1, which can significantly enhance [Ca2+]i and result in Ca2+ overload in bladder ICC-LCs, indicating that the Piezo1 channel and NCX1 are potential novel therapeutic targets for chronic cystitis-associated bladder hyperactivity. A protein that controls the passage of ions through cell membranes is implicated in interstitial cystitis/painful bladder syndrome (IC/PBS). This condition causes chronic pelvic pain and increased urinary frequency and urgency. Current treatment options are unsatisfactory. Researchers led by Longkun Li at the Third Military Medical University in Chongqing, China, and Mingjia Tan at the University of Michigan, Ann Arbor, USA, studied the role of this membrane channel protein, called Piezo1. Increased activity of Piezo1 was linked to bladder hyperactivity in rats with drug-induced cystitis. The research also identified a synergistic interaction between Piezo1 and a second membrane channel protein. A drug that inhibits Piezo1 activity reduced bladder hyperactivity in the rats. Drugs targeting these two proteins might help to treat the chronic cystitis of patients with IC/PBS.
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