Protective role of low-dose TGF-β1 in early diabetic nephropathy induced by streptozotocin

- Low-dose TGF-β1 improved metabolic disorder and renal damage in diabetic nephropathy (DN).
- Mechanisms include attenuating oxidative stress, maintaining Stat3, and balancing Treg/Th17.
- Low-dose anti-IL-6Rα mAb alone or together with low-dose TGF-β1 did not attenuated DN.

ObjectiveTo 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).MethodsDiabetes 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.ResultsLow-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.ConclusionsThis 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.