Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China.
Int Immunopharmacol. 2013 Nov;17(3):752-8. doi: 10.1016/j.intimp.2013.08.023. Epub 2013 Sep 18.
To determine whether low-dose TGF-β1 and/or IL-6-receptorα monoclonal antibody (anti-IL-6Rα) can be used to delay renal damage and preserve renal function by rebalancing regulatory T (Treg)/Th17 cells during the course of early diabetic nephropathy (DN) induced by streptozotocin (STZ).
Diabetes was induced in C57BL/6 mice by multiple STZ injection. Low-dose TGF-β1 (0.1 μg/mouse/week) and/or anti-IL-6Rα (10 μg/mouse/week) were administered 6 dozes after STZ injection. After 40 days of diabetes onset, metabolic indices, renal structure, activated Akt and Stat3, Treg/Th17 balance, markers and inflammatory cytokines, and oxidative stress in glomeruli were assessed.
Low-dose TGF-β1, instead of causing renal damage, decreased blood glucose, ameliorated kidney hypertrophy, attenuated oxidative stress, maintained activated Stat3, and induced Treg/Th17 balance in early DN. Interestingly, low-dose TGF-β1+anti-IL-6Rα or anti-IL-6Rα alone did not attenuate DN.
This study provides convincing experimental evidence of the protective effects of low-dose TGF-β1 in improving metabolic disorder and slowing renal damage in early DN.
通过在链脲佐菌素（STZ）诱导的早期糖尿病肾病（DN）过程中重新平衡调节性 T（Treg）/Th17 细胞，确定低剂量 TGF-β1 和/或白细胞介素 6 受体α 单克隆抗体（抗 IL-6Rα）是否可用于延迟肾损伤并维持肾功能。
通过多次 STZ 注射诱导 C57BL/6 小鼠发生糖尿病。在 STZ 注射后 6 剂给予低剂量 TGF-β1（0.1 μg/只/周）和/或抗 IL-6Rα（10 μg/只/周）。在糖尿病发病 40 天后，评估代谢指标、肾脏结构、活化的 Akt 和 Stat3、Treg/Th17 平衡、标志物和炎症细胞因子以及肾小球中的氧化应激。
低剂量 TGF-β1 没有引起肾损伤，反而降低了血糖，改善了肾脏肥大，减轻了氧化应激，维持了活化的 Stat3，并在早期 DN 中诱导了 Treg/Th17 平衡。有趣的是，低剂量 TGF-β1+抗 IL-6Rα 或单独使用抗 IL-6Rα 并不能减轻 DN。
这项研究为低剂量 TGF-β1 在改善早期 DN 代谢紊乱和减缓肾损伤方面的保护作用提供了令人信服的实验证据。
