title: Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type II diabetes mice.
abstract: 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-1β, tumor necrosis factor α (TNF-α). The conditioned media (CM) of MIF-activated macrophages and TNF-α 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.
authors: School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors: Zhigang
authors: Z
authors: Wang
authors: Meng
authors: M
authors: Wei
authors: Meng
authors: M
authors: Wang
authors: Lei
authors: L
authors: Chen
authors: Hua
authors: H
authors: Liu
authors: Yi
authors: Y
authors: Ren
authors: Kehui
authors: K
authors: Shi
authors: Hongli
authors: H
authors: Jiang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D001786:Blood Glucose; D007555:Isoxazoles; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse