Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Biomed Pharmacother. 2023 May;161:114450. doi: 10.1016/j.biopha.2023.114450. Epub 2023 Feb 28.
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide and the prevalence of DKD has increased over recent decades. Inflammation is involved in the development and progression of DKD. In this study, we explored the potential role of macrophage inflammatory protein-1β (MIP-1β) in DKD. Clinical non-diabetic subjects and DKD patients with different levels of urine albumin-to-creatinine ratio (ACR) were enrolled in the study. Lepr/ mice and MIP-1β knockout mice were also used as mouse models for DKD. We found that serum MIP-1β levels were elevated in the DKD patients, especially those with ACRs that were less than or equal to 300, suggesting that MIP-1β is activated in clinical DKD. The administration of anti-MIP-1β antibodies attenuated DKD severity in the Lepr/ mice, which also showed reduced glomerular hypertrophy and podocyte injury, as well as decreased inflammation and fibrosis, suggesting that MIP-1β plays a role in the development of DKD. The MIP-1β knockout mice showed improved renal function and decreased renal glomerulosclerosis and fibrosis in DKD. Furthermore, podocytes from the MIP-1β knockout mice showed less high glucose-induced inflammation and fibrosis compared to those from wild-type mice. In conclusion, the inhibition or deletion of MIP-1β protected podocytes, modulated renal inflammation, and ameliorated experimental DKD, suggesting that novel anti-MIP-1β strategies could potentially be used to treat DKD.
糖尿病肾病（DKD）是全球终末期肾病的主要病因，近年来其患病率有所增加。炎症参与了 DKD 的发生和发展。在这项研究中，我们探讨了巨噬细胞炎性蛋白-1β（MIP-1β）在 DKD 中的潜在作用。本研究纳入了临床非糖尿病患者和不同尿白蛋白与肌酐比值（ACR）水平的 DKD 患者。莱普/小鼠和 MIP-1β 敲除小鼠也被用作 DKD 的小鼠模型。我们发现，DKD 患者的血清 MIP-1β 水平升高，尤其是 ACR 小于或等于 300 的患者，提示 MIP-1β在临床 DKD 中被激活。抗 MIP-1β 抗体的给药减轻了 Lepr/小鼠的 DKD 严重程度，这也表明肾小球肥大和足细胞损伤减少，炎症和纤维化减少，提示 MIP-1β在 DKD 的发生发展中起作用。MIP-1β 敲除小鼠在 DKD 中表现出改善的肾功能和减少的肾小球硬化和纤维化。此外，与野生型小鼠相比，MIP-1β 敲除小鼠的足细胞在高葡萄糖诱导的炎症和纤维化方面较少。总之，抑制或删除 MIP-1β可保护足细胞，调节肾脏炎症，并改善实验性 DKD，提示新型抗 MIP-1β 策略可能用于治疗 DKD。
