All-trans-Retinoic Acid Inhibits the Development of Mesangial Proliferative Glomerulonephritis in Interleukin-6 Transgenic Mice
All-trans-Retinoic Acid Inhibits the Development of Mesangial Proliferative Glomerulonephritis in Interleukin-6 Transgenic Mice
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DOI：
10.1159/000084655
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发表时间：
2005-03
影响因子：
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通讯作者：
Y. Shima;M. Iwano;K. Yoshizaki;Toshio Tanaka;I. Kawase;N. Nishimoto
中科院分区：
文献类型：
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作者：
Y. Shima;M. Iwano;K. Yoshizaki;Toshio Tanaka;I. Kawase;N. Nishimoto
全反式维甲酸（All-trans-retinoic acid，ATRA）是一种维生素A衍生物，可抑制白细胞介素6（interleukin-6，IL-6）的产生，并下调IL-6受体（IL-6 R）和/或其信号转导糖蛋白130。本研究观察了ATRA对IL-6转基因小鼠系膜增生性肾小球肾炎（PGN）的体内抗肾炎作用及对大鼠系膜细胞增殖的体外抑制作用。IL-6转基因小鼠的体内实验表明，ATRA给药抑制蛋白尿和血尿，降低IL-6浓度;此外，组织学检查表明，它改善PGN。在体外实验中，使用大鼠肾小球系膜细胞表明，ATRA抑制细胞生长的剂量依赖性的方式从10-4至10- 6 M的范围内。ATRA的这种抑制作用部分被IL-6的加入所抵消。RT-PCR结果显示，ATRA还能降低系膜细胞IL-6 R的表达，但对系膜细胞糖蛋白130的表达无明显影响。这些发现表明，通过阻断IL-6功能，ATRA可能对PGN有治疗作用。
All-trans-retinoic acid (ATRA), a vitamin A derivative, was reported to suppress the interleukin-6 (IL-6) production and to downregulate the IL-6 receptor (IL-6R) and/or its signal transducer glycoprotein 130. We investigated the in vivo antinephritic effect of ATRA on IL-6 transgenic mice which had developed mesangial proliferative glomerulonephritis (PGN) as well as its in vitro inhibitory effect on the proliferation of rat mesangial cells. In vivo experiments on IL-6 transgenic mice showed that ATRA administration suppressed proteinuria and hematuria and reduced the IL-6 concentrations; furthermore, histological examination demonstrated that it improved PGN. In vitro experiments using rat mesangial cells demonstrated that ATRA inhibited cell growth in a dose-dependent manner within a range from 10–4 to 10–6M. This inhibition by ATRA was partially counteracted by the addition of IL-6. RT-PCR assay results showed that ATRA also reduced IL-6R, but not the glycoprotein 130 expression in mesangial cells. These findings indicate that, by blocking of the IL-6 function, ATRA may be therapeutically effective in PGN.