PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis
Prokineticin 2 (PK2) is a novel chemokine-like peptide with multiple proinflammatory and nociception-related activities. This study aimed to explore the potential role of PK2 in modulating bladder activity and sensation in rats with cyclophosphamide- (CYP-) induced cystitis. Changes of PK2 and proki...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/289519 |
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| author | Biao Chen Huiping Zhang Lili Liu Jiaojiao Wang Zhangqun Ye |
| author_facet | Biao Chen Huiping Zhang Lili Liu Jiaojiao Wang Zhangqun Ye |
| author_sort | Biao Chen |
| collection | DOAJ |
| description | Prokineticin 2 (PK2) is a novel chemokine-like peptide with multiple proinflammatory and nociception-related activities. This study aimed to explore the potential role of PK2 in modulating bladder activity and sensation in rats with cyclophosphamide- (CYP-) induced cystitis. Changes of PK2 and prokineticin receptors (PKRs) in normal and inflamed urinary bladders were determined at several time points (4 h, 48 h, and 8 d) after CYP treatment. Combining a nonselective antagonist of prokineticin receptors (PKRA), we further evaluated the regulatory role of PK2 in modulating bladder function and visceral pain sensation via conscious cystometry and pain behavioral scoring. PK2 and prokineticin receptor 1 (PKR1), but not prokineticin receptor 2, were detected in normal and upregulated in CYP-treated rat bladders at several levels. Immunohistochemistry staining localized PKR1 primarily in the urothelium. Blocking PKRs with PKRA showed no effect on micturition reflex activity and bladder sensation in control rats while it increased the voiding volume, prolonged voiding interval, and ameliorated visceral hyperalgesia in rats suffering from CYP-induced cystitis. In conclusion, PK2/PKR1 signaling pathway contributes to the modulation of inflammation-mediated voiding dysfunction and spontaneous visceral pain. Local blockade of PKRs may represent a novel and promising therapeutic strategy for the clinical management of inflammation-related bladder diseases. |
| format | Article |
| id | doaj-art-71dbea4cccd1458bae4ee841be7ccb50 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-71dbea4cccd1458bae4ee841be7ccb502025-08-20T03:33:42ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/289519289519PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced CystitisBiao Chen0Huiping Zhang1Lili Liu2Jiaojiao Wang3Zhangqun Ye4Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaFamily Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Pathology, Wuhan Women and Children’s Medical Center, Wuhan 430016, ChinaFamily Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaProkineticin 2 (PK2) is a novel chemokine-like peptide with multiple proinflammatory and nociception-related activities. This study aimed to explore the potential role of PK2 in modulating bladder activity and sensation in rats with cyclophosphamide- (CYP-) induced cystitis. Changes of PK2 and prokineticin receptors (PKRs) in normal and inflamed urinary bladders were determined at several time points (4 h, 48 h, and 8 d) after CYP treatment. Combining a nonselective antagonist of prokineticin receptors (PKRA), we further evaluated the regulatory role of PK2 in modulating bladder function and visceral pain sensation via conscious cystometry and pain behavioral scoring. PK2 and prokineticin receptor 1 (PKR1), but not prokineticin receptor 2, were detected in normal and upregulated in CYP-treated rat bladders at several levels. Immunohistochemistry staining localized PKR1 primarily in the urothelium. Blocking PKRs with PKRA showed no effect on micturition reflex activity and bladder sensation in control rats while it increased the voiding volume, prolonged voiding interval, and ameliorated visceral hyperalgesia in rats suffering from CYP-induced cystitis. In conclusion, PK2/PKR1 signaling pathway contributes to the modulation of inflammation-mediated voiding dysfunction and spontaneous visceral pain. Local blockade of PKRs may represent a novel and promising therapeutic strategy for the clinical management of inflammation-related bladder diseases.http://dx.doi.org/10.1155/2015/289519 |
| spellingShingle | Biao Chen Huiping Zhang Lili Liu Jiaojiao Wang Zhangqun Ye PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis Mediators of Inflammation |
| title | PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis |
| title_full | PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis |
| title_fullStr | PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis |
| title_full_unstemmed | PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis |
| title_short | PK2/PKR1 Signaling Regulates Bladder Function and Sensation in Rats with Cyclophosphamide-Induced Cystitis |
| title_sort | pk2 pkr1 signaling regulates bladder function and sensation in rats with cyclophosphamide induced cystitis |
| url | http://dx.doi.org/10.1155/2015/289519 |
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