title: The c-Jun N-terminal kinase (JNK) pathway is activated in human interstitial cystitis (IC) and rat protamine sulfate induced cystitis.
abstract: The pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) is currently unclear. However, inflammation has been suggested to play an important role in BPS/IC. JNK downstream signaling plays an important role in numerous chronic inflammatory diseases. However, studies of the JNK pathway in BPS/IC are limited. In this study, we investigated the role of the JNK pathway in human BPS/IC and rat protamine sulfate (PS)-induced cystitis and examined the effect of the selective JNK inhibitor SP600125 on rat bladder cystitis. In our study, we demonstrated that the JNK signaling pathway was activated (the expression of JNK, c-Jun, p-JNK, p-c-Jun, IL-6 and TNF-α were significantly increasing in BPS/IC compared to the non-BPS/IC patients) and resulted in inflammation in human BPS/IC. Further animal models showed that the JNK pathway played an important role in the pathogenesis of cystitis. JNK inhibitors, SP600125, effectively inhibited the expression of p-JNK, p-c-Jun, IL-6 and TNF-α. The inhibition of these pathways had a protective effect on PS-induced rat cystitis by significantly decreasing histological score and mast cell count and improving bladder micturition function (micturition frequency significantly decreasing and bladder capacity significantly increasing). Therefore, JNK inhibition could be used as a potential treatment for BPS/IC.
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Departments of Urology, Cancer Institute/Cancer Hospital, Chongqing, 400030, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Xingyou
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Qina
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Qingjian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Longkun
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers; D001706:Biopsy; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D010766:Phosphorylation; D011479:Protamines / Q000009:adverse effects; D051381:Rats
chemical_list: D015415:Biomarkers; D016207:Cytokines; D011479:Protamines; D048031:JNK Mitogen-Activated Protein Kinases