Macrophages in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury
Macrophages in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury
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DOI：
10.1111/j.1523-1755.2004.00367.x
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发表时间：
2004-01-01
影响因子：
19.6
通讯作者：
Tesch, GH
中科院分区：
文献类型：
--
作者：
Chow, F;Ozols, E;Tesch, GH
背景巨噬细胞介导的肾损伤与肾小球肾炎的进展形式有关;然而，巨噬细胞在2型糖尿病肾病（终末期肾衰竭的主要原因）中的作用尚未确定。因此，我们研究了巨噬细胞是否可以促进db/db小鼠2型糖尿病肾病的进展。在8月龄时具有不同血糖和脂质水平的db/db小鼠中检查肾损伤的发生率。在2、4、6和8月龄的正常db/+和糖尿病db/db小鼠中分析肾损伤与肾脏巨噬细胞积聚的相关性。在db/db小鼠中，白蛋白尿和血浆肌酐升高与血糖和血红蛋白A（1c）（HbA（1c））水平升高相关，但与肥胖或高脂血症无关。db/db小鼠中进行性糖尿病肾病与肾脏巨噬细胞增加相关。db/db小鼠中的巨噬细胞蓄积和巨噬细胞活化与高血糖、HbA 1c水平、白蛋白尿、血浆肌酐升高、肾小球和肾小管损伤、肾纤维化和巨噬细胞趋化因子[单核细胞趋化蛋白-1（MCP-1）、骨桥蛋白、迁移抑制因子（MIF）、单核细胞集落刺激因子（M-CSF）]的肾脏表达相关。肾小球巨噬细胞的聚集和活化也与肾小球IgG和C3沉积的增加相关，而肾小球IgG和C3沉积本身依赖于高血糖。肾脏巨噬细胞蓄积与db/db小鼠2型糖尿病肾病进展相关。糖尿病db/db肾脏中的巨噬细胞积聚和激活与长期高血糖、肾小球免疫复合物沉积和肾脏趋化因子产生增加有关，并增加了针对糖尿病肾病中巨噬细胞介导的损伤的特定疗法的可能性。
Background. Macrophage-mediated renal injury has been implicated in progressive forms of glomerulonephritis; however, a role for macrophages in type 2 diabetic nephropathy, the major cause of end-stage renal failure, has not been established. Therefore, we examined whether macrophages may promote the progression of type 2 diabetic nephropathy in db/db mice.Methods. The incidence of renal injury was examined in db/db mice with varying blood sugar and lipid levels at 8 months of age. The association of renal injury with the accumulation of kidney macrophages was analyzed in normal db/+ and diabetic db/db mice at 2, 4, 6, and 8 months of age.Results. In db/db mice, albuminuria and increased plasma creatinine correlated with elevated blood glucose and hemoglobin A(1c) (HbA(1c)) levels but not with obesity or hyperlipidemia. Progressive diabetic nephropathy in db/db mice was associated with increased kidney macrophages. Macrophage accumulation and macrophage activation in db/db mice correlated with hyperglycemia, HbA1c levels, albuminuria, elevated plasma creatinine, glomerular and tubular damage, renal fibrosis, and kidney expression of macrophage chemokines [monocyte chemoattractant protein-1 (MCP-1), osteopontin, migration inhibitory factor (MIF), monocyte-colony-stimulating factor (M-CSF)]. The accrual and activation of glomerular macrophages also correlated with increased glomerular IgG and C3 deposition, which was itself dependent on hyperglycemia.Conclusion. Kidney macrophage accumulation is associated with the progression of type 2 diabetic nephropathy in db/db mice. Macrophage accumulation and activation in diabetic db/db kidneys is associated with prolonged hyperglycemia, glomerular immune complex deposition, and increased kidney chemokine production, and raises the possibility of specific therapies for targeting macrophage-mediated injury in diabetic nephropathy.