title: Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways.
abstract: BACKGROUND
  Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development.
  
  
  METHODS
  In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters.
  
  
  RESULTS
  Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Specifically, gene expression analysis demonstrated that at day 0 the RAS system is involved. This is altered at day 6, when Wnt signaling and focal adhesion pathways are affected. However, at and after 24 days, proliferation, apoptosis, altered ECM signaling and many other factors become involved.
  
  
  CONCLUSIONS
  Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation.
authors.affiliation: Department of Biological Sciences, University of Cyprus.
authors.forename: Panayiota
authors.initials: P
authors.lastname: Koupepidou
authors.forename: Kyriacos N
authors.initials: KN
authors.lastname: Felekkis
authors.forename: Bettina
authors.initials: B
authors.lastname: Kränzlin
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
mesh_terms: D000818:Animals; D002455:Cell Division; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D022001:Focal Adhesions / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008297:Male; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012084:Renin-Angiotensin System / Q000502:physiology; D050396:TRPP Cation Channels / Q000235:genetics* / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D050396:TRPP Cation Channels; D051153:Wnt Proteins
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