Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy.
BACKGROUND
Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury.


METHODS
CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death.


RESULTS
Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3).


CONCLUSIONS
rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.
Lee
Seung Hun
SH
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Li
Can
C
Lim
Sun Woo
SW
Ahn
Kyung Ohk
KO
Choi
Bum Soon
BS
Kim
Yong Soo
YS
Moon
In Sung
IS
Kim
Jin
J
Bang
Byung Kee
BK
Yang
Chul Woo
CW
D000818:Animals; D017209:Apoptosis; D002097:C-Reactive Protein / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000188:drug therapy*; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D004921:Erythropoietin; D016572:Cyclosporine; D002097:C-Reactive Protein