title: Effect of FTY720 on chronic cyclosporine nephropathy in rats.
abstract: BACKGROUND
  Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy.
  
  
  METHODS
  Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.5 mg/kg), or both CsA and FTY720 (0.125 mg/kg). The effects of FTY720 on CsA-induced renal injury were evaluated using renal function tests and histopathology, and the expression of mediators of CsA-induced renal injury (osteopontin, transforming growth factor-beta1 [TGF-beta1], betaig-h3, and angiotensin II).
  
  
  RESULTS
  FTY720 treatment significantly decreased T-lymphocyte accumulation in kidneys compared with CsA treatment alone. FTY720 treatment improved not only CsA-induced renal dysfunction but also renal histopathology, demonstrated by decreased macrophage infiltration and interstitial fibrosis. Increased osteopontin, TGF-beta1, betaig-h3, and angiotensin II expression in CsA-treated rat kidneys were decreased with FTY720 treatment.
  
  
  CONCLUSIONS
  FTY720 treatment prevents CsA-induced renal injury.
authors.affiliation: Xenotransplantation Center, Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea, and Department of Internal Medicine, The Affiliated Hospital, YanBian University Medical College, JiLin, China.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Jung Shim
authors.initials: JS
authors.lastname: Kim
authors.forename: Kyung Ohk
authors.initials: KO
authors.lastname: Ahn
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Yang
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000473:pathology; D008297:Male; D053495:Osteopontin; D011409:Propylene Glycols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D000099222:betaIG-H3 Protein
chemical_list: D000804:Angiotensin II; D016572:Cyclosporine; D016326:Extracellular Matrix Proteins; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents; D053495:Osteopontin; D011409:Propylene Glycols; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D013110:Sphingosine; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099222:betaIG-H3 Protein; C506897:Spp1 protein, rat; C508962:Tgfb1 protein, rat