Nakamura T, Fukui M, Ebihara I, Osada S, Nagaoka I, Tomino Y, Koide H
Department of Medicine and Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.
Diabetes. 1993 Mar;42(3):450-6. doi: 10.2337/diab.42.3.450.
Evaluations of glomerular mRNA levels encoding for PCNA, TNF-alpha, PDGF-A and -B chains, TGF-beta, IGF-I, bFGF, and EGF were made at 4, 12, and 24 wk after injection of STZ in Sprague-Dawley rats. The mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF increased with age in STZ-induced diabetic rats. At 24 wk after STZ injection, mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF were increased 3.8-fold, (P < 0.01), 4.2-fold (P < 0.01), 4.0-fold (P < 0.01), 5.2-fold (P < 0.001), and 3.6-fold (P < 0.01), respectively, in the glomeruli of diabetic rats when compared with control rats. In contrast, mRNA levels for IGF-I, PDGF-A chain, and EGF were not altered in glomeruli from diabetic and control rats throughout the experimental period. Insulin treatment partially ameliorated the increase in mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF in the glomeruli of diabetic rats. These data indicate that alterations in growth factor mRNA levels in glomeruli may be a manifestation of diabetic nephropathy, and that hyperglycemia or insulin deficiency may play a role in abnormal growth factor gene regulation.
在给斯普拉格-道利大鼠注射链脲佐菌素(STZ)后的4周、12周和24周,对编码增殖细胞核抗原(PCNA)、肿瘤坏死因子-α(TNF-α)、血小板衍生生长因子-A(PDGF-A)和-B(PDGF-B)链、转化生长因子-β(TGF-β)、胰岛素样生长因子-I(IGF-I)、碱性成纤维细胞生长因子(bFGF)和表皮生长因子(EGF)的肾小球mRNA水平进行了评估。在STZ诱导的糖尿病大鼠中,PCNA、TNF-α、PDGF-B链、TGF-β和bFGF的mRNA水平随年龄增加。在注射STZ后24周,与对照大鼠相比,糖尿病大鼠肾小球中PCNA、TNF-α、PDGF-B链、TGF-β和bFGF的mRNA水平分别增加了3.8倍(P < 0.01)、4.2倍(P < 0.01)、4.0倍(P < 0.01)、5.2倍(P < 0.001)和3.6倍(P < 0.01)。相比之下,在整个实验期间,糖尿病大鼠和对照大鼠肾小球中IGF-I、PDGF-A链和EGF的mRNA水平没有改变。胰岛素治疗部分改善了糖尿病大鼠肾小球中PCNA、TNF-α、PDGF-B链、TGF-β和bFGF的mRNA水平升高。这些数据表明,肾小球中生长因子mRNA水平的改变可能是糖尿病肾病的一种表现,并且高血糖或胰岛素缺乏可能在异常的生长因子基因调控中起作用。