Department of Pathology, Hebei Medical University, Shijiazhuang, PR China.
Am J Nephrol. 2010;31(5):380-8. doi: 10.1159/000286559. Epub 2010 Mar 19.
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.
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-beta1 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.
Urine albumin excretion and renal hypertrophy were alleviated in diabetic mice by overexpression of SOCS-1. The expression of TGF-beta1 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.
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.
Janus 激酶（JAK）/信号转导和转录激活因子（STAT）参与糖尿病肾病的发生。细胞因子信号转导抑制因子-1（SOCS-1）是 JAK/STAT 信号通路的负反馈调节因子之一。本研究旨在探讨 SOCS-1 对糖尿病肾病中 JAK/STAT 通路和单核细胞趋化蛋白-1（MCP-1）表达的影响。
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 载体治疗 4 周，并与年龄匹配的非糖尿病小鼠进行比较。评估功能性和病理标志物、单核细胞趋化蛋白-1（MCP-1）和转化生长因子-β1（TGF-β1）的表达以及 STAT1 和 STAT3 的磷酸化。还观察了 SOCS-1 对高糖条件下系膜细胞 MCP-1 表达的影响。
SOCS-1 的过表达减轻了糖尿病小鼠的尿白蛋白排泄和肾脏肥大。SOCS-1 的基因转染显著抑制了糖尿病肾脏中 TGF-β1 和 MCP-1 的表达以及 STAT1 和 STAT3 的激活。在培养的系膜细胞中，SOCS-1 的过表达显著抑制了高糖诱导的 MCP-1 表达。
本研究表明，SOCS-1 可能通过改善 MCP-1 表达和调节糖尿病小鼠 JAK/STAT 的磷酸化来减轻肾脏损伤。
