Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy
Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy
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DOI：
10.1016/j.etp.2009.02.068
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Yatomi, Yutaka
中科院分区：
文献类型：
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作者：
Imasawa, Toshiyuki;Kitamura, Hiroshi;Yatomi, Yutaka
1-磷酸鞘氨醇（Sph-I-P）通过其受体如S1 P1和S1 P2调节血管稳态。S1 P1具有保护血管的作用，而S1 P2具有拮抗作用，因此，S1 P1和S1 P2的平衡决定了血管通透性的调节。在糖尿病肾病中，典型的病理变化之一是内皮损伤，这可能是血管通透性改变的结果。因此，我们推测S1 P1和S1 P2的表达平衡在糖尿病肾病的肾小球中变得不适当。为了验证这一假设，在注射一年后分析了5只注射链脲佐菌素诱导的糖尿病SD大鼠和6只仅注射溶剂的对照大鼠。糖尿病大鼠肾小球内皮损伤。实时荧光定量PCR分析显示，糖尿病大鼠肾皮质S1 P2/S1 P1 mRNA比值明显高于非糖尿病对照组。免疫组化显示S1 P1主要表达于肾小球内皮细胞和系膜细胞，而S1 P2主要表达于肾小球系膜细胞。此外，在糖尿病大鼠肾小球中S1 P2与S1 P1的染色强度的比率显著升高。表达PDGF-B的细胞的数量也高于对照组，PDGF-B可增强S1 P2的表达。总之，在糖尿病肾病大鼠的肾小球中，Sph-1-P信号优先通过S1 P2而不是S1 P1传递。这种Sph-1-P信号的不平衡传递可能参与了内皮损伤的发病机制。（C）2009 Elsevier GmbH。All rights reserved.
Sphingosine 1-phosphate (Sph-1-P) regulates vascular homeostasis through its receptors like S1P1 and S1P2. While S1P1 works to protect vasculature, S1P2 works antagonistically against it. Therefore, the balance of S1P1 and S1P2 determines the regulation of vascular permeability. In diabetic nephropathy, one of the typical pathological changes is endothelial injury possibly as a result of changes in vascular permeability. Therefore, we hypothesized that the balance of S1P1 and S1P2 expression becomes inappropriate in glomeruli of diabetic nephropathy. To verify the hypothesis, five SD rats with diabetes induced by streptozotocin injection and six control rats injected with only the vehicle were analyzed one year after injection. The glomeruli of the diabetic rats exhibited endothelial injuries. The analysis by realtime PCR revealed that the ratio of S1P2/S1P1 m RNA in the renal cortex of the diabetic rats was significantly higher than that In the non-diabetic control group. Immunohistochemistry revealed that S1P1 was expressed by endothelial and mesangial cells, while S1P2 was mainly expressed by mesangial cells in glomeruli. Furthermore, the ratio of the staining intensity of S1P2 to that of S1P1 in the glomeruli was significantly higher in the diabetic rats. The number of cells expressing PDGF-B, which enhances S1P2 expression, was also higher in the glomeruli of the diabetic rats than in the controls. In conclusion, Sph-1-P signals are preferentially transmitted through S1P2, rather than S1P1, in the glomneruli of rats with diabetic nephropathy. Such unbalanced delivery of the Sph-1-P signals might be involved ill the pathogenesis of endothelial injuries. (C)2009 Elsevier GmbH. All rights reserved.