Macrophages in diabetic nephropathy in patients with type 2 diabetes
Macrophages in diabetic nephropathy in patients with type 2 diabetes
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DOI：
10.1093/ndt/gfw260
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发表时间：
2017-08-01
影响因子：
6.1
通讯作者：
IJpelaar, Daphne H. T.
中科院分区：
文献类型：
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作者：
Klessens, Celine Q. F.;Zandbergen, Malu;IJpelaar, Daphne H. T.
背景资料。炎症在2型糖尿病肾病的发生发展中起着重要作用。虽然在糖尿病肾病的实验模型中已发现巨噬细胞，但对糖尿病肾病患者中巨噬细胞的存在知之甚少。因此，我们研究了糖尿病肾病患者肾小球和间质巨噬细胞的存在和表型与临床和组织病理学参数的关系。肾尸检标本取自88例经组织学证实为糖尿病肾病的2型糖尿病患者，用CD68和CD163作为巨噬细胞的一般标志和M2/抗炎标志物进行染色。根据糖尿病肾病的组织病理学分级对肾脏损害进行评分。对照肾脏尸检样本来自无肾脏异常的患者和无糖尿病肾病的患者。计数每肾小球阳性细胞数。对间质巨噬细胞进行半定量计数。各组均可见巨噬细胞。糖尿病肾病组肾小球CD68(+)细胞数和CD163(+)细胞数分别为4.2(0~19)个和2.1(0~14.47)个。在所有组织病理级别之间的分布是相似的。肾小球CD163(+)巨噬细胞与糖尿病肾病分级、肾间质纤维化、肾小管萎缩、肾小球硬化呈正相关。间质CD68_巨噬细胞与肾小球滤过率、分期及蛋白尿相关。我们的结果表明，在2型糖尿病肾病患者和对照组的肾小球和间质中存在巨噬细胞。尽管患者和对照组的肾小球巨噬细胞数量相似，但肾小球抗炎CD163(+)巨噬细胞与糖尿病肾病的病理损害相关。结合间质巨噬细胞与间质纤维化、肾小管萎缩、糖尿病肾病分级及肾功能的相关性，提示巨噬细胞在糖尿病肾病进展中可能起一定作用。因此，靶向巨噬细胞可能是抑制糖尿病肾病进展的一种有前景的新疗法。
Background. Inflammation plays a role in the development of diabetic nephropathy (DN) in type 2 diabetes. Although macrophages have been found in experimental models of DN, little is known regarding the presence of macrophages in patients with DN. Therefore, we investigated the presence and phenotype of glomerular and interstitial macrophages in relation to clinical and histopathological parameters in patients with DN.Methods. Renal autopsy samples were obtained from 88 type 2 diabetic patients with histologically proven DN and stained for CD68 and CD163 as general and M2/anti-inflammatory markers of macrophages. Renal damage was scored based on histopathological classification of DN. Control renal autopsy samples were obtained from patients without renal abnormalities and from diabetic patients without DN. Positive cells per glomerulus were counted. Interstitial macrophages were counted semi-quantitatively.Results. Macrophages were present in all groups. In the DN group, the mean number of CD68(+) cells per glomerulus and CD163(+) cells per glomerulus was 4.2 (range 0-19) and 2.1 (range 0-14.47), respectively. The distribution was similar between all histopathological classes. Glomerular CD163(+) macrophages were positively associated with DN class, interstitial fibrosis and tubular atrophy, and glomerulosclerosis. Interstitial CD68_ macrophages were correlated with glomerular filtration rate stage and albuminuria.Conclusions. Our results demonstrate that macrophages are present in the glomeruli and interstitium of type 2 diabetic patients with DN and of controls. Although patients and controls had similar numbers of glomerular macrophages, glomerular anti-inflammatory CD163(+) macrophages were associated with pathological lesions in DN. Taken together with the correlation between interstitial macrophages and interstitial fibrosis and tubular atrophy, DN class, and renal function, this finding suggests that macrophages may play a role in DN progression. Therefore, targeting macrophages may be a promising new therapy for inhibiting the progression of DN.