Department of Hemodialysis, Qilu Hospital, Shandong University, Jinan, China.
Inflammation. 2015 Oct;38(5):1739-47. doi: 10.1007/s10753-015-0151-z.
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.
作为糖尿病的最重要的长期并发症之一，糖尿病肾病（DN）是糖尿病患者终末期肾病和高死亡率的主要原因。长 pentraxin 3（Ptx3）是一个保守蛋白超家族的成员，其特征是具有环状多聚体结构和保守的 C 末端结构域。多项临床研究表明，血浆 Ptx3 水平升高与心血管疾病和慢性肾脏病（CKD）有关。然而，Ptx3 对 DN 的治疗作用从未被研究过。在我们目前的研究中，我们表明 Ptx3 在减轻 DN 中的肾损伤中起着关键作用。在我们的小鼠高血糖诱导的肾病模型中，与对照组相比，Ptx3 治疗组的nephrin、乙酰化 nephrin 和 Wilm's 肿瘤-1 蛋白（WT-1）的表达明显增加。与对照组相比，DN 中 Ptx3 治疗组的 CD4(+)T 细胞、CD8(+)T 细胞、Ly6G(+)中性粒细胞和 CD11b(+)巨噬细胞的数量均显著降低。IL-4 和 IL-13 水平在 Ptx3 治疗组明显高于对照组。相应地，与对照组相比，Ptx3 治疗组 Arg1 或 CD206 表达的巨噬细胞数量增加。此外，抑制 Ptx3 治疗的巨噬细胞可消除 Ptx3 治疗引起的肾损伤减轻。总之，Ptx3 通过促进 M2 巨噬细胞分化来减轻 DN 中的肾损伤。
