Effect of methylprednisolone on transforming growth factor-beta, insulin-like growth factor-I, and basic fibroblast growth factor gene expression in the kidneys of NZB/W F1 mice.
The present study was carried out to determine whether transforming growth factor-beta, insulin-like growth factor-I and basic fibroblast growth factor mRNA levels were correlated with disease activity in NZB/W F1 mice, an animal model of systemic lupus erythematosus. Levels of mRNA for these three growth factors increased significantly as nephritis progressed in these mice. At 48 weeks of age, transforming growth factor-beta, insulin-like growth factor-I, and basic fibroblast growth factor mRNA levels showed a 11- (p < 0.001), 10- (p < 0.001), and 8-fold (p < 0.001) increase, respectively, in the renal cortex of NZB/W F1 mice when compared with NZW control mice. In NZW kidneys, these mRNA levels showed little change throughout the study period. At 24 weeks of age, NZB/W F1 mice were divided in 2 groups that received either methylprednisolone or saline injections for 24 weeks. The development of histological lesions and the increase in these growth factor mRNA levels in the kidneys of NZB/W F1 mice were both suppressed by methylprednisolone. These results indicate that the transforming growth factor-beta, insulin-like growth factor and basic fibroblast growth factor may play a role in the progression of murine lupus nephritis and that methylprednisolone may be an effective treatment at the transcription level of these growth factor genes for this type of nephritis.
Nakamura
T
T
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Ebihara
I
I
Nagaoka
I
I
Osada
S
S
Tomino
Y
Y
Koide
H
H
D000818:Animals; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D008775:Methylprednisolone