Suppressor of Cytokine Signaling-1 Ameliorates Expression of MCP-1 in Diabetic Nephropathy
Suppressor of Cytokine Signaling-1 Ameliorates Expression of MCP-1 in Diabetic Nephropathy
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细胞因子信号转导 1 的抑制剂可改善糖尿病肾病中 MCP-1 的表达
DOI：
10.1159/000286559
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发表时间：
2010-03
影响因子：
4.2
通讯作者：
Duan, Huijun
中科院分区：
文献类型：
--
作者：
Shi, Yonghong;Du, Chunyang;Zhang, Yanling;Ren, Yunzhuo;Hao, Jun;Zhao, Song;Yao, Fang;Duan, Huijun
背景：Janus激酶（JAK）/信号转导和转录激活因子（STAT）参与糖尿病肾病。细胞因子信号转导抑制因子-1（SOCS-1）是JAK/STAT信号转导的负反馈调节因子之一。本研究探讨了SOCS-1对糖尿病肾病JAK/STAT通路和MCP-1表达的影响。研究方法：链脲佐菌素诱导的糖尿病小鼠接受pEF-FLAG-I/mSOCS-1质粒或pEF-FLAG-I载体4周，并与年龄匹配的非糖尿病小鼠进行比较。评估功能和病理标志物、单核细胞趋化蛋白-1（MCP-1）和TGF-β1的表达以及STAT 1和STAT 3的磷酸化。SOCS-1对高糖条件下系膜细胞MCP-1表达的影响也进行了检测。结果：过表达SOCS-1可减轻糖尿病小鼠尿白蛋白排泄和肾脏肥大。SOCS-1基因转染可显著抑制糖尿病大鼠肾脏TGF-β1和MCP-1的表达及STAT 1和STAT 3的活化。在培养的系膜细胞中，SOCS-1的过表达显著抑制高糖诱导的MCP-1表达。结论：本研究提示，SOCS-1可能通过改善MCP-1的表达和调节JAK/STAT的磷酸化而减轻糖尿病小鼠的肾损害。
Background: Janus kinase (JAK)/signal transducers and activators of transcription (STAT) contribute to diabetic nephropathy. Suppressor of cytokine signaling-1 (SOCS-1) is one of the negative feedback regulators of JAK/STAT signaling. This study investigated the effect of SOCS-1 on the JAK/STAT pathway and MCP-1 expression in diabetic nephropathy. Methods: Streptozotocin-induced diabetic mice received pEF-FLAG-I/mSOCS-1 plasmid or pEF-FLAG-I vector for 4 weeks and were compared with age-matched nondiabetic mice. Functional and pathologic markers, expression of monocyte chemoattractant protein-1 (MCP-1) and TGF-β1 and phosphorylation of STAT1 and STAT3 were assessed. The effect of SOCS-1 on the expression of MCP-1 in mesangial cells under high glucose conditions was also examined.Results: Urine albumin excretion and renal hypertrophy were alleviated in diabetic mice by overexpression of SOCS-1. The expression of TGF-β1 and MCP-1 and the activation of STAT1 and STAT3 were significantly inhibited in diabetic kidney by gene delivery of SOCS-1. In cultured mesangial cells, overexpression of SOCS-1 markedly suppressed high glucose-induced MCP-1 expression. Conclusions: This study suggests that SOCS-1 may attenuate renal damage by ameliorating MCP-1 expression and regulation of the phosphorylation of JAK/STAT in diabetic mice.
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影响因子：
7.7
作者：
H. Makino;N. Kashihara;H. Sugiyama;K. Kanao;T. Sekikawa;K. Okamoto;Y. Maeshima;Z. Ota;R. Nagai
通讯作者：
H. Makino;N. Kashihara;H. Sugiyama;K. Kanao;T. Sekikawa;K. Okamoto;Y. Maeshima;Z. Ota;R. Nagai
影响因子：
1.6
作者：
S. Nicholas
通讯作者：
S. Nicholas
影响因子：
6.1
作者：
Yang, Niansheng;Luo, Mingqian;Yu, Xueqing
通讯作者：
Yu, Xueqing
影响因子：
4.2
作者：
Watanabe, S;Mu, W;Johnson, RJ
通讯作者：
Johnson, RJ
影响因子：
4.4
作者：
Z. Bian;V. Elner;Ayako Yoshida;S. L. Kunkel;S. Elner
通讯作者：
Z. Bian;V. Elner;Ayako Yoshida;S. L. Kunkel;S. Elner