Nakamura T, Ebihara I, Fukui M, Tomino Y, Koide H
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Kidney Int. 1991 Nov;40(5):874-81. doi: 10.1038/ki.1991.288.
We examined the effects of methylprednisolone (MPSL) on type IV collagen, laminin and heparan sulfate proteoglycan (HSPG) mRNA levels in the renal glomeruli and medulla of puromycin aminonucleoside (PAN) nephrosis. mRNA levels encoding for type IV collagen and laminin increased markedly, whereas those for HSPG decreased significantly in glomeruli of PAN nephrosis. Administration of MPSL partially ameliorated the abnormal gene expression for basement membrane components. Furthermore, we showed that medullary mRNA levels for all these basement membrane components decreased with age in PAN nephrosis with or without MPSL treatment, suggesting that neither PAN nor MPSL has any effect on basement membrane component mRNA levels in the renal medulla. In contrast, mRNA levels for the interstitial collagens including alpha 1 (I) and alpha 1 (III) chains in glomeruli showed little change with or without MPSL treatment, whereas those in medulla increased significantly in PAN nephrosis when compared with the control. MPSL ameliorated the abnormal gene expression of alpha 1 (I) and alpha 1 (III) collagen in renal medulla. These results indicate that PAN affects both glomerular mRNA encoding for basement membrane components and medullary mRNA encoding for interstitial collagens, and that MPSL has marked effects on the amelioration of abnormal gene expression in both glomeruli and medulla of PAN nephrosis.
我们研究了甲基强的松龙(MPSL)对嘌呤霉素氨基核苷(PAN)肾病大鼠肾小球和髓质中IV型胶原、层粘连蛋白和硫酸乙酰肝素蛋白聚糖(HSPG)mRNA水平的影响。在PAN肾病大鼠的肾小球中,编码IV型胶原和层粘连蛋白的mRNA水平显著升高,而HSPG的mRNA水平则显著降低。给予MPSL可部分改善基底膜成分的异常基因表达。此外,我们发现,无论是否接受MPSL治疗,PAN肾病大鼠髓质中所有这些基底膜成分的mRNA水平均随年龄增长而降低,这表明PAN和MPSL对肾髓质中基底膜成分的mRNA水平均无影响。相比之下,无论是否接受MPSL治疗,肾小球中包括α1(I)和α1(III)链在内的间质胶原的mRNA水平变化不大,而与对照组相比,PAN肾病大鼠髓质中的间质胶原mRNA水平显著升高。MPSL改善了肾髓质中α1(I)和α1(III)胶原的异常基因表达。这些结果表明,PAN影响肾小球中编码基底膜成分的mRNA和髓质中编码间质胶原的mRNA,且MPSL对改善PAN肾病大鼠肾小球和髓质中的异常基因表达具有显著作用。