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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China.
Xiaodong
X
Ma
Jingjing
J
Ding
Haiyan
H
Min
Yanting
Y
Wen
Qian
Q
Gao
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt
Diabetic nephropathy; IL-6 blockade; Regulatory T cells; Streptozotocin; TGF-β1; Th17 cells