Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney
Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney
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DOI：
10.1007/s10157-012-0625-3
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发表时间：
2012-04
影响因子：
2.3
通讯作者：
Ryo Nagase;Nobuo Kajitani;K. Shikata;D. Ogawa;Ryo Kodera;S. Okada;Y. Kido;H. Makino
中科院分区：
文献类型：
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作者：
Ryo Nagase;Nobuo Kajitani;K. Shikata;D. Ogawa;Ryo Kodera;S. Okada;Y. Kido;H. Makino
研究背景炎症反应参与了糖尿病肾病的发病过程，但糖尿病肾病中巨噬细胞的活化及表型变化尚不清楚。唾液酸粘附素是含有17个细胞外免疫球蛋白样结构域的巨噬细胞粘附分子，并且是与造血细胞上表达的唾液酸配体结合的I型凝集素。本研究的目的是阐明巨噬细胞的活化和表型变化在糖尿病肾病的进展，方法我们检测了泛巨噬细胞，驻地巨噬细胞，唾液酸粘附素，主要组织相容性复合物II类和α-平滑肌肌动蛋白的表面标志物在糖尿病大鼠肾小球的表达，在0，1，4，12，和链脲佐菌素诱导糖尿病后24周。同时检测IV型胶原的表达及系膜基质面积的变化。的机制为上调表达的唾液酸粘附素对巨噬细胞invitro.ResultsThe巨噬细胞的数量增加，在糖尿病诱导后1个月，糖尿病肾小球和增加的数量一直维持到6个月。另一方面，糖尿病晚期，唾液酸粘附素阳性的巨噬细胞增多，伴随着α-平滑肌肌动蛋白阳性的系膜细胞、系膜基质面积和IV型胶原的增加。IL-1 β和肿瘤坏死因子-α刺激巨噬细胞可诱导唾液酸粘附素基因表达，而IL-4、转化生长因子-β和高糖对唾液酸粘附素基因表达无影响。
BackgroundInflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy.MethodsWe examined the expression of surface markers for pan-macrophages, resident macrophages, sialoadhesin, major histocompatibility complex class II and α-smooth muscle actin in the glomeruli of diabetic rats using immunohistochemistry at 0, 1, 4, 12, and 24 weeks after induction of diabetes by streptozotocin. Expression of type IV collagen and the change of mesangial matrix area were also measured. The mechanism for up-regulated expression of sialoadhesin on macrophages was evaluated in vitro.ResultsThe number of macrophages was increased in diabetic glomeruli at 1 month after induction of diabetes and the increased number was maintained until 6 months. On the other hand, sialoadhesin-positive macrophages were increased during the late stage of diabetes concomitantly with the increase of α-smooth muscle actin-positive mesangial cells, mesangial matrix area and type IV collagen. Gene expression of sialoadhesin was induced by stimulation with interleukin (IL)-1β and tumor necrosis factor-α but not with IL-4, transforming growth factor-β and high glucose in cultured human macrophages.ConclusionThe present findings suggest that sialoadhesin-positive macrophages may contribute to the progression of diabetic nephropathy.