title: Reduction of osteopontin in vivo inhibits tubular epithelial to mesenchymal transition in rats with chronic allograft nephropathy.
abstract: OBJECTIVE
  Chronic allograft nephropathy (CAN) is an important etiological factor causing graft loss. However, the mechanism of CAN is unclear. Osteopontin (OPN), a proinflammatory and profibrosis molecule, plays a key role in late stages of renal diseases. We investigated the potential role of OPN in the pathogenesis of CAN.
  
  
  METHODS
  Using a F344 to Lewis rat CAN model, we injected short hairpin RNA (shRNA) constructs targeting OPN or negative control plasmids through the renal vein following electroporation. At 12 weeks after the transplantation, we determined interstitial fibrosis (IF) and tubular atrophy (TA) of the tubular epithelial cells (TECs). OPN expression was examined using Western blots and immunohistochemistry (IHC). Molecules involved in epithelial to mesenchymal transition (EMT) of TECs were examined using IHC and Western blots.
  
  
  RESULTS
  OPN expression in kidney grafts was decreased by the RNA interference (RNAi) group. Histology observations showed IF and TA to be mild with stable renal function in the RNAi-treated group. EMT of TECs was significantly lessened after reducing OPN.
  
  
  CONCLUSIONS
  Reduction of OPN in vivo inhibited progression of CAN. OPN may be of therapeutic value in transplantation settings.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Deng
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Ying
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Gu
mesh_terms: D000818:Animals; D001284:Atrophy; D015153:Blotting, Western; D015536:Down-Regulation; D018274:Electroporation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D018014:Gene Transfer Techniques; D006085:Graft Survival; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D034741:RNA, Small Interfering; C506897:Spp1 protein, rat; D053495:Osteopontin