Background/aims

The theory of inflammation is one of the important theories in the pathogenesis of diabetic nephropathy (DN). We herein aimed to explore whether loganin affected macrophage infiltration and activation upon diabetic nephropathy (DN) by a spontaneous DN mice and a co-culture system of glomerular mesangial cells (GMCs) and macrophage cells (RAW264.7) which was induced by advanced glycation end products (AGEs).

Methods and key findings

Loganin showed remarkable capacity on protecting renal from damage by mitigating diabetic symptoms, improving the histomorphology of the kidney, decreasing the expression of extracellular matrix such as FN, COL-IV and TGF-β, reversing the production of IL-12 and IL-10 and decreasing the number of infiltrating macrophages in the kidney. Moreover, loganin showed markedly effects by suppressing iNOS and CD16/32 expressions (M1 markers), increasing Arg-1 and CD206 expressions (M2 markers), which were the phenotypic transformation of macrophage. These effects may be attributed to the inhibition of the receptor for AGEs (RAGE) /monocyte chemotactic protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2) signaling pathway, with significantly down-regulated expressions of RAGE, MCP-1 and CCR2 by loganin. Loganin further decreased MCP-1 secretion when RAGE was silenced, which means other target was involved in regulating the MCP-1 expression. While loganin combinated with the inhibitor of CCR2 exerted stronger anti-inhibition effects of iNOS expression, suggesting that CCR2 was the target of loganin in regulating the activation of macrophages.

Significance

Loganin could ameliorate DN kidney damage by inhibiting macrophage infiltration and activation via the MCP-1/CCR2 signaling pathway in DN.

中文翻译：

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Loganin 通过抑制糖尿病肾病中的 MCP-1/CCR2 轴减轻巨噬细胞浸润和活化

背景/目标

炎症学说是糖尿病肾病（DN）发病机制中的重要理论之一。我们在此旨在探讨马钱素是否影响自发性 DN 小鼠和由晚期糖基化诱导的肾小球系膜细胞 (GMC) 和巨噬细胞 (RAW264.7) 的共培养系统对糖尿病肾病 (DN) 的巨噬细胞浸润和活化。最终产品（AGEs）。

方法和主要发现

Loganin 通过减轻糖尿病症状、改善肾脏组织形态学、降低细胞外基质如 FN、COL-IV 和 TGF-β 的表达，逆转 IL-12 和 IL-10 的产生，显示出显着的保护肾脏免受损害的能力并减少肾脏中浸润性巨噬细胞的数量。此外，马钱素通过抑制 iNOS 和 CD16/32 表达（M1 标记），增加 Arg-1 和 CD206 表达（M2 标记）显示出显着效果，这些是巨噬细胞的表型转化。这些作用可能是由于AGEs受体（RAGE）/单核细胞趋化蛋白-1（MCP-1）/CC趋化因子受体2（CCR2）信号通路的抑制，RAGE、MCP-1的表达显着下调和登录名的 CCR2。当 RAGE 被沉默时，Loganin 进一步降低了 MCP-1 的分泌，这意味着其他靶标参与了调节 MCP-1 的表达。而马钱素与CCR2抑制剂的组合对iNOS表达具有更强的抗抑制作用，提示CCR2是马钱素调控巨噬细胞活化的靶点。

意义

Loganin 可通过 DN 中的 MCP-1/CCR2 信号通路抑制巨噬细胞浸润和活化来改善 DN 肾损伤。