title: Platelet Derived Growth Factor Has a Role in Pressure Induced Bladder Smooth Muscle Cell Hyperplasia and Acts in a Paracrine Way.
abstract: OBJECTIVE
  Bladder outlet obstruction is a finding in many urological disorders, leading to bladder wall hyperplasia. We investigated platelet derived growth factor and its receptor in human bladder smooth muscle cells and urothelial cells exposed to hydrostatic pressure or PDGF in vitro.
  
  
  METHODS
  Bladder smooth muscle cells and urothelial cells were exposed to elevated hydrostatic pressure for 1 hour. The expression of PDGF and PDGFR was evaluated using reverse transcriptase-polymerase chain reaction and Western blot analysis. Pressure or PDGF induced proliferation of bladder smooth muscle cells with or without pretreatment with lovastatin or imatinib was measured by enzyme-linked immunosorbent assay. PDGFRα was knocked down with siRNA.
  
  
  RESULTS
  After hydrostatic pressure bladder smooth muscle cells showed increased PDGFRα and β expression. PDGF was not expressed in bladder smooth muscle cells. Urothelial cells showed no expression of PDGFR but PDGF expression was noted. Western blot analysis of bladder smooth muscle cells revealed a pressure induced increase in PDGFR in the membrane fraction. Phosphorylation of PDGFR occurred with pressure induction. Bladder smooth muscle cell proliferation was increased in pressure and PDGF mediated fashion. Pretreatment with lovastatin or imatinib prevented proliferation. There was no cell proliferation after PDGFRα knockdown.
  
  
  CONCLUSIONS
  Increased expression and phosphorylation of PDGFR in bladder smooth muscle cells after hydrostatic pressure suggests a pivotal role of the PDGF pathway in pressure induced hyperplasia of bladder smooth muscle cells. PDGF expressed in urothelial cells may act in a paracrine way. Cholesterol depletion, inhibition of receptor tyrosine kinase activity and knockdown of PDGFRα in bladder smooth muscle cells prevent pressure and PDGF mediated cell proliferation. Targeting PDGFR seems a promising way to influence pressure induced bladder wall hyperplasia.
authors.affiliation: Department of Anaesthesiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Preis
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Herlemann
authors.affiliation: Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Adam
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Dietz
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Kappler
authors.affiliation: Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; Department of Pediatric Surgery and Urology, Cnopf'sche Kinderklinik, Nuremberg, Germany. Electronic address: maximilian.stehr@diakonieneuendettelsau.de.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stehr
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002648:Child; D055785:Gene Knockdown Techniques; D006801:Humans; D006874:Hydrostatic Pressure; D006965:Hyperplasia; D000068877:Imatinib Mesylate / Q000494:pharmacology; D066298:In Vitro Techniques; D008148:Lovastatin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology*; D019899:Paracrine Communication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology*; D001748:Urinary Bladder Neck Obstruction / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014563:Urodynamics / Q000502:physiology*
chemical_list: D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D000068877:Imatinib Mesylate; D008148:Lovastatin; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: gene knockdown techniques; hyperplasia; muscle; platelet-derived growth factor alpha; receptor; smooth; urinary bladder