title: Connexin26 is regulated in rat urothelium by the scaffold protein IB1/JIP-1.
abstract: Proper function of the wall of bladder requires gap junctional communication for coordinating the responses of smooth muscle (SMC) and urothelial cells exposed to urine pressure. In the rat bladder, Cx43 is expressed by SMC and urothelial cells, whereas Cx26 expression is restricted to the epithelium. We used a model of bladder outlet obstruction, in which a ligature is placed around the urethra to increase voiding pressure. Increased fluid pressure was associated with increased Cx43 and Cx26 mRNA expression and with the activation of a signaling cascade including the transcription factor c-Jun, which is a component of the AP-1 complex. The signaling pathway of the c-Jun NH2 terminal kinase (JNK) requires the presence of the scaffold protein Islet-Brain1/c-Jun amino-terminal kinase Interacting Protein-1 (IB1/JIP-1). Under stress conditions resulting from urine retention, we have found a reduced content of IB1/JIP-1 in urothelial cells, which in turn induced a drastic increase of JNK and AP-1 binding activities. The stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1, using a viral gene transfer approach, a condition which also resulted in a decrease in Cx26 mRNA. The data show that: 1) mechanical stress of urothelial cells activates in vivo JNK, as a consequence of a regulated expression of IB1/JIP-1 and 2) that urothelial Cx26 may be directly regulated by the AP-1 complex.
authors.affiliation: Service of Urology, University Hospital, Lausanne, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Tawadros
authors.forename: P
authors.initials: P
authors.lastname: Meda
authors.forename: H J
authors.initials: HJ
authors.lastname: Leisinger
authors.forename: G
authors.initials: G
authors.lastname: Waeber
authors.forename: J A
authors.initials: JA
authors.lastname: Haefliger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D000072259:Connexin 26; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014524:Urethral Obstruction; D019459:Urothelium / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018031:Connexin 43; D017630:Connexins; D004268:DNA-Binding Proteins; C000607042:GJB2 protein, human; C000607044:Gjb2 protein, rat; C490666:MAPK8IP1 protein, human; C110528:Mapk8ip1 protein, rat; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D000072259:Connexin 26; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases