Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation
Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation
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DOI：
10.1007/s10753-015-0151-z
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发表时间：
2015-10-01
期刊：
影响因子：
5.1
通讯作者：
Yang, Xiangdong
中科院分区：
文献类型：
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作者：
Sun, Huaibin;Tian, Jun;Yang, Xiangdong
糖尿病肾病（diabetic nephropathy，DN）是糖尿病最重要的远期并发症之一，是糖尿病患者终末期肾病和高死亡率的主要原因。长五聚体蛋白3（Ptx 3）是一个保守的蛋白质超家族成员，其特征在于环状多聚体结构和保守的C-末端结构域。几项临床研究表明，血浆Ptx 3水平升高与心血管疾病和慢性肾脏疾病（CKD）相关。然而，Ptx 3对DN的治疗作用从未被研究过。在我们目前的研究中，我们显示了Ptx 3在减轻DN肾损伤中的关键作用。在我们的小鼠高血糖诱导的肾病模型中，与对照相比，Ptx 3治疗显示nephrin、乙酰化nephrin和Wilm's tumor-1蛋白（WT-1）的表达显着增加。Ptx 3治疗组DN患者外周血CD 4 + T细胞、CD 8 + T细胞、Ly 6 G+中性粒细胞和CD 11b+巨噬细胞数量均显著低于对照组。Ptx 3治疗组IL-4、IL-13水平明显高于对照组。相应地，与对照组相比，Ptx 3处理组显示Arg 1或CD 206表达巨噬细胞的数量增加。此外，抑制Ptx 3处理的巨噬细胞消除了Ptx 3处理诱导的减轻的肾损伤。结论：Ptx 3通过促进M2巨噬细胞分化减轻DN肾损害。
As one of the most important long-term complications of diabetes, diabetic nephropathy (DN) is the major cause of end-stage renal disease and high mortality in diabetic patients. The long pentraxin 3 (Ptx3) is a member of a superfamily of conserved proteins characterized by a cyclic multimeric structure and a conserved C-terminal domain. Several clinical investigations have demonstrated that elevated plasma Ptx3 levels are associated with cardiovascular and chronic kidney diseases (CKD). However, the therapeutic effect of Ptx3 on DN has never been investigated. In our current study, we showed a crucial role for Ptx3 in attenuating renal damage in DN. In our mouse hyperglycemia-induced nephropathy model, Ptx3 treatment showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with control. The number of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils, and CD11b(+) macrophages were all significantly lower in the Ptx3-treated group than that in the control group in DN. The IL-4 and IL-13 levels in the Ptx3-treated group were markedly higher than that in the control group in DN. Correspondingly, the Ptx3-treated group showed increased numbers of Arg1- or CD206-expressing macrophages compared with the control group. Furthermore, inhibition of Ptx3-treated macrophages abrogated the alleviated renal damage induced by Ptx3 treatment. In conclusion, Ptx3 attenuates renal damage in DN by promoting M2 macrophage differentiation.