Effect of FTY720 on chronic cyclosporine nephropathy in rats.
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.
Kim
Jin Young
JY
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.
Lim
Sun Woo
SW
Li
Can
C
Kim
Jung Shim
JS
Ahn
Kyung Ohk
KO
Yang
Hyun Joo
HJ
Choi
Bum Soon
BS
Kim
Yong Soo
YS
Kim
Jin
J
Bang
Byung Kee
BK
Yang
Chul Woo
CW
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
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