Triptolide Suppresses Glomerular Mesangial Cell Proliferation in Diabetic Nephropathy Is Associated with Inhibition of PDK1/Akt/mTOR Pathway

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2017 Nov 7

PMID 29104493

Citations 26

Authors

Fei Han

Mei Xue

Yunpeng Chang

Xiaoyu Li

Yang Yang

Bei Sun

Liming Chen

Affiliations

Soon will be listed here.

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.

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