Inhibition of Macrophage Migration Inhibitory Factor Reduces Diabetic Nephropathy in Type II Diabetes Mice

被引：71

作者：

Wang, Zhigang ^{[1
]}

Wei, Meng ^{[1
]}

Wang, Meng ^{[2
]}

Chen, Lei ^{[1
]}

Liu, Hua ^{[2
]}

Ren, Yi ^{[2
]}

Shi, Kehui ^{[2
]}

Jiang, Hongli ^{[2
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Med, Xian 710061, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Dialysis Dept, Nephrol Ctr, Affiliated Hosp 1,Med Sch, Xian 710061, Shaanxi, Peoples R China

来源：

INFLAMMATION | 2014年 / 37卷 / 06期

关键词：

nephropathy; diabetes; macrophage; macrophage inhibitory factor; TAUTOMERASE ACTIVE-SITE; RECEPTOR CD74; EXPRESSION; MIF; INFLAMMATION; RESPONSES; BINDING; TARGET;

D O I：

10.1007/s10753-014-9934-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Macrophage migration inhibitory factor (MIF) plays a critical role in inflammation and is elevated in diabetic kidney. However, whether MIF plays a causative role in diabetic nephropathy (DN) remains unclear. In the present study, we have demonstrated that after treatment of 8-week-old diabetic db/db and nondiabetic db/m mice with the MIF inhibitor ISO-1 (20 mg/kg) for 8 weeks, there was a significant decrease in blood glucose, albuminuria, extracellular matrix accumulation, epithelial-mesenchymal transition (EMT), and macrophage activation in the kidney of db/db mice. Incubation of macrophages with MIF induced the production of proinflammatory cytokines, including interleukin (IL) 6, IL-1 beta, tumor necrosis factor alpha (TNF-alpha). The conditioned media (CM) of MIF-activated macrophages and TNF-alpha induced by MIF caused podocyte damage. Moreover, CM from MIF-activated macrophages induced EMT of renal tubular cells, and this effect was blocked by ISO-1. Thus, MIF inhibition may be a potential therapeutic strategy for DN. This effect may be attributable to its inhibitory effect on macrophage activation in the diabetic kidney.

引用

页码：2020 / 2029

页数：10

共 41 条

[1]

ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis [J].