ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2017; 13(10):1266-1275. doi:10.7150/ijbs.20485 This issue Cite
Research Paper
Triptolide Suppresses Glomerular Mesangial Cell Proliferation in Diabetic Nephropathy Is Associated with Inhibition of PDK1/Akt/mTOR Pathway
Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University
Abstract
Mesangial cell proliferation has been identified as a mainly contributing factor to glomerulosclerosis, which is typical of diabetic nephropathy. However, the specific mechanisms and therapies remain unclear. PDK1 is a critical regulator of cell proliferation, but the specific role of PDK1 in diabetic nephropathy has not been fully illuminated. In the current study, we demonstrated that triptolide (TP) ameliorated albuminuria in the high fat diet/STZ-induced diabetic rats. TP also suppressed the increased proliferating cell markers Ki-67 and PCNA in the kidney tissues. Our results of MTT and cell cycle analysis further confirmed that TP significantly inhibited mesangial cell proliferation, and the inhibition of PDK1/Akt/mTOR pathway might be the underlying mechanisms. In addition, we also found that the PDK1 activator (PS48) could reverse the cell proliferation inhibition role of TP. These data suggest that TP may be useful in prevention of diabetic glomerulosclerosis and that PDK1/Akt/mTOR pathway might be the underlying mechanism.
Keywords: Diabetic nephropathy, Mesangial cell, Proliferation, PDK1, Triptolide.
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