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: Jin Young Kim, Sun Woo Lim, Can Li, Jung Shim Kim, Kyung Ohk Ahn, Hyun Joo Yang, Bum Soon Choi, Yong Soo Kim, Jin Kim, Byung Kee Bang, Chul Woo Yang
• Journal: Transplantation (Transplantation) Vol. 80 Issue 9 Pg. 1323-30 (Nov 15 2005) ISSN: 0041-1337 [Print] United States
• PMID: 16314802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Immunosuppressive Agents
• Propylene Glycols
• RNA, Messenger
• Sialoglycoproteins
• Spp1 protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Osteopontin
• Angiotensin II
• betaIG-H3 protein
• Cyclosporine
• Fingolimod Hydrochloride
• Sphingosine

Topics

• Angiotensin II (metabolism)
• Animals
• Chronic Disease
• Cyclosporine (adverse effects)
• Extracellular Matrix Proteins (metabolism)
• Fibrosis
• Fingolimod Hydrochloride
• Immunosuppressive Agents (adverse effects, pharmacology)
• Kidney (pathology)
• Kidney Diseases (chemically induced, metabolism, pathology, prevention & control)
• Lymphocytes (drug effects)
• Macrophages (pathology)
• Male
• Osteopontin
• Propylene Glycols (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sialoglycoproteins (genetics)
• Sphingosine (analogs & derivatives)
• T-Lymphocytes (pathology)
• Transforming Growth Factor beta (genetics, metabolism)
• Transforming Growth Factor beta1