Induction of PPAR gamma mRNA and protein expression by rosiglitazone in chronic cyclosporine nephropathy in the rat.
OBJECTIVE
We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPARgamma) expression in an experimental model of chronic cyclosporine (CsA) nephropathy.


METHODS
Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15mg/kg per day) for 28 days, and control rats were treated with vehicle (VH group, olive oil 1mL/kg per day) for 28 days. RGTZ (3mg/kg) was concurrently administered via gavage to the CsA and VH groups. Expression of PPARgamma mRNA and protein was evaluated with RT-PCR, immunohistochemistry, and immunoblotting.


RESULTS
PPARgamma mRNA expression was similar to the level of PPARgamma protein constitutively expressed in the kidneys of the VH treated rats, with expression in the glomerular epithelial, distal tubular cells, and collecting tubular cells. PPARgamma protein expression in CsA-treated rat kidneys was significantly less than in the VH group. However, concomitant administration of RGTZ restored PPARgamma protein expression in the kidneys of the CsA- reated rats.


CONCLUSIONS
Exogenous administration of RGTZ treatment upregulates PPARgamma expression and that this mechanism may play a role in protecting against CsA-induced renal injury.
Ahn
Kyung Ohk
KO
Department of Internal Medicine, Kangnam St Mary's Hospital, 505 Banpo-Dong, Seocho-Gu, Seoul, Korea.
Lim
Sun Woo
SW
Yang
Hyun Joo
HJ
Li
Can
C
Sugawara
Akira
A
Ito
Sadayoshi
S
Choi
Bum Soon
BS
Kim
Yong Soo
YS
Kim
Jin
J
Yang
Chul Woo
CW
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D047495:PPAR gamma / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016572:Cyclosporine