title: Early activation of fibrogenesis in transplanted kidneys: a study on serial renal biopsies.
abstract: OBJECTIVE
  In kidney transplants, the renin-angiotensin system (RAS) is involved in systemic and local changes that may induce fibrosis. Our aim was to use gene expression and immunohistochemical analysis to investigate the RAS and several factors involved in the fibrogenic cascade in allograft biopsies.
  
  
  METHODS
  We considered 43 donor biopsies (T0), 18 biopsies obtained for diagnostic purposes (Td) and 24 protocol biopsies (Tp) taken 2 months after transplantation in patients with stable renal function. Morphometric alpha SMA and TGF beta 1 analysis, and Masson's Trichrome staining were performed. mRNA levels of angiotensinogen, renin, ACE, AT1-R, AT2-R, TGF beta 1, BMP-7, Coll III, fibronectin and alpha SMA were analyzed by real-time RT/PCR. MDRD a year after the transplant was also considered.
  
  
  RESULTS
  Significantly higher levels of AT1-R and alpha SMA transcripts were found in Tp than in T0. Regression analysis showed significant TGF beta 1-independent positive correlations between RAS and matrix components in T0 and Tp, but more evident in Tp, where a positive correlation between TGF beta 1 and Masson's Trichrome stained areas was also seen.
  
  
  CONCLUSIONS
  Our results suggest that RAS and TGF beta 1-related fibrogenic loops are activated as early as 2 months after kidney transplantation.
authors.affiliation: Nephrology Division, Department of Medical and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy. dorella.delprete@unipd.it
authors.forename: Dorella
authors.initials: D
authors.lastname: Del Prete
authors.forename: Monica
authors.initials: M
authors.lastname: Ceol
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.forename: Daniela
authors.initials: D
authors.lastname: Vianello
authors.forename: Emilia
authors.initials: E
authors.lastname: Tiralongo
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Romina
authors.initials: R
authors.lastname: Graziotto
authors.forename: Luciana
authors.initials: L
authors.lastname: Bonfante
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scaparrotta
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Furian
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
authors.forename: Angela
authors.initials: A
authors.lastname: D'Angelo
mesh_terms: D000328:Adult; D001706:Biopsy; D005355:Fibrosis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000473:pathology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012084:Renin-Angiotensin System / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1