title: Urea transporter UT-B deletion induces DNA damage and apoptosis in mouse bladder urothelium.
abstract: BACKGROUND
  Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line.
  
  
  RESULTS
  Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis.
  
  
  CONCLUSIONS
  UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Zixun
authors.initials: Z
authors.lastname: Dong
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ran
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Jihui
authors.initials: J
authors.lastname: Chen
authors.forename: Tianluo
authors.initials: T
authors.lastname: Lei
authors.forename: Weiling
authors.initials: W
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.forename: Lise
authors.initials: L
authors.lastname: Bankir
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001120:Arginine / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014508:Urea / Q000378:metabolism / Q000494:pharmacology; D001743:Urinary Bladder / Q000378:metabolism* / Q000648:ultrastructure; D019459:Urothelium / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D026901:Membrane Transport Proteins; C452857:urea transporter B, mouse; D009569:Nitric Oxide; D014508:Urea; D001120:Arginine