title: Down-regulation of annexin A1 in the urothelium decreases cell survival after bacterial toxin exposure.
abstract: OBJECTIVE
  We examined the role of annexins in bladder urothelium. We characterized expression and distribution in normal bladders, biopsies from patients with bladder pain syndrome, cultured human urothelium and urothelial TEU-2 cells.
  
  
  METHODS
  Annexin expression in bladder layers was analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunofluorescence. We assessed cell survival after exposure to the pore forming bacterial toxin streptolysin O by microscopy and alamarBlue® assay. Bladder dome biopsies were obtained from 8 asymptomatic controls and 28 patients with symptoms of bladder pain syndrome.
  
  
  RESULTS
  Annexin A1, A2, A5 and A6 were differentially distributed in bladder layers. Annexin A6 was abundant in detrusor smooth muscle and low in urothelium, while annexin A1 was the highest in urothelium. Annexin A2 was localized to the lateral membrane of umbrella cells but excluded from tight junctions. TEU-2 cell differentiation caused up-regulation of annexin A1 and A2 and down-regulation of annexin A6 mRNA. Mature urothelium dedifferentiation during culture caused the opposite effect, decreasing annexin A1 and increasing annexin A6. Annexin A2 influenced TEU-2 cell epithelial permeability. siRNA mediated knockdown of annexin A1 in TEU-2 cells caused significantly decreased cell survival after streptolysin O exposure. Annexin A1 was significantly reduced in biopsies from patients with bladder pain syndrome.
  
  
  CONCLUSIONS
  Several annexins are expressed in human bladder and TEU-2 cells, in which levels are regulated during urothelial differentiation. Annexin A1 down-regulation in patients with bladder pain syndrome might decrease cell survival and contribute to compromised urothelial function.
authors: Urology Research Laboratory, Department of Clinical Research, University of Bern, Bern, Switzerland. monastyk@dkf.unibe.ch
authors: Katia
authors: K
authors: Monastyrskaya
authors: Eduard B
authors: EB
authors: Babiychuk
authors: Annette
authors: A
authors: Draeger
authors: Fiona C
authors: FC
authors: Burkhard
mesh_terms: D000704:Analysis of Variance; D017305:Annexin A1 / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured / Q000187:drug effects; D018856:Cystitis, Interstitial / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D018709:Statistics, Nonparametric; D013301:Streptolysins / Q000494:pharmacology*; D014162:Transfection; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000473:pathology*
chemical_list: D017305:Annexin A1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013301:Streptolysins