高迁移率族蛋白 B1 在糖尿病肾病发展中的作用。
The role of high-mobility group box-1 protein in the development of diabetic nephropathy.
机构信息
Diabetic Complications Research Center, Division of Traditional Korean Medicine Integrated Research, Korea Institute of Oriental Medicine, Daejeon, South Korea.
出版信息
Am J Nephrol. 2011;33(6):524-9. doi: 10.1159/000327992. Epub 2011 May 23.
BACKGROUND/AIMS: The purpose of the experiment reported here was to assess the involvement of high-mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE) and nuclear factor (NF)-κB signaling pathway in the development of rat diabetic nephropathy.
METHODS
Diabetes was induced by intraperitoneal streptozotocin injection in 7-week-old male rats. At 20 weeks of age, renal expression of HMGB1 was detected by immunohistochemistry. The expression of RAGE and NF-κB activity was studied by Western blot and electrophoretic mobility shift assay in renal tissues of normoglycemic and diabetic rats, respectively.
RESULTS
HMGB1 was highly expressed in both the cytoplasmic and nuclear patterns in diabetic renal glomerular cells and tubular epithelial cells, although in normal rats, HMGB1 was expressed only in the cell nuclei. The expression of RAGE, a potential receptor for HMGB1, and NF-κB activity were also greater in diabetic than in normal rats. Moreover, diabetes increased the binding of NF-κB to the RAGE promoter.
CONCLUSION
These findings suggest that hyperglycemia-induced HMGB1 release may induce the renal injury in diabetic rats, and that the pathogenic role of HMGB1 might be dependent on RAGE and through activation of NF-κB.
背景/目的：本实验旨在评估高迁移率族蛋白 B1（HMGB1）、晚期糖基化终产物受体（RAGE）和核因子（NF）-κB 信号通路在大鼠糖尿病肾病发展中的作用。
方法
通过腹腔注射链脲佐菌素诱导 7 周龄雄性大鼠产生糖尿病。20 周龄时，通过免疫组织化学检测 HMGB1 在肾脏中的表达。通过 Western blot 和电泳迁移率变动分析分别研究正常血糖和糖尿病大鼠肾脏组织中 RAGE 和 NF-κB 活性的表达。
结果
糖尿病大鼠肾小球细胞和肾小管上皮细胞的细胞质和核内均高度表达 HMGB1，而在正常大鼠中，HMGB1 仅表达于细胞核内。RAGE 的表达和 NF-κB 活性在糖尿病大鼠中也高于正常大鼠。此外，糖尿病增加了 NF-κB 与 RAGE 启动子的结合。
结论
这些发现表明，高血糖诱导的 HMGB1 释放可能导致糖尿病大鼠的肾脏损伤，而 HMGB1 的致病作用可能依赖于 RAGE，并通过 NF-κB 的激活。
Zotero 插件