Triptolide Suppresses Glomerular Mesangial Cell Proliferation in Diabetic Nephropathy Is Associated with Inhibition of PDK1/Akt/mTOR Pathway.
Triptolide Suppresses Glomerular Mesangial Cell Proliferation in Diabetic Nephropathy Is Associated with Inhibition of PDK1/Akt/mTOR Pathway.
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雷公藤甲素抑制糖尿病肾病肾小球系膜细胞增殖与抑制 PDK1/Akt/mTOR 通路相关
DOI：
10.7150/ijbs.20485
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发表时间：
2017
影响因子：
9.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Han F;Xue M;Chang Y;Li X;Yang Y;Sun B;Chen L
系膜细胞增殖被认为是糖尿病肾病典型的肾小球硬化的一个主要因素。然而，具体的机制和治疗方法仍不清楚。PDK1是细胞增殖的重要调节因子，但其在糖尿病肾病中的具体作用尚未完全阐明。在本研究中，我们证明了雷公藤甲素(TP)改善了高脂饮食/STZ诱导的糖尿病大鼠的蛋白尿。茶多酚还能抑制肾组织中增殖细胞标志物Ki-67和增殖细胞核抗原的表达。四甲基偶氮唑盐比色法和细胞周期分析进一步证实茶多酚抑制系膜细胞增殖，抑制PDK1/Akt/mTOR通路可能是其作用机制之一。此外，我们还发现PDK1激活剂(PS48)可以逆转TP对细胞增殖的抑制作用。提示TP可能是预防糖尿病肾小球硬化的有效途径，而PDK1/Akt/mTOR通路可能是其机制之一。
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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影响因子：
7.7
作者：
Kawano Y;Nakae J;Watanabe N;Fujisaka S;Iskandar K;Sekioka R;Hayashi Y;Tobe K;Kasuga M;Noda T;Yoshimura A;Onodera M;Itoh H
通讯作者：
Itoh H
影响因子：
9
作者：
Saurus P;Kuusela S;Lehtonen E;Hyvönen ME;Ristola M;Fogarty CL;Tienari J;Lassenius MI;Forsblom C;Lehto M;Saleem MA;Groop PH;Holthöfer H;Lehtonen S
通讯作者：
Lehtonen S
影响因子：
6.1
作者：
Gao, Qing;Shen, Wenwen;Liu, Zhihong
通讯作者：
Liu, Zhihong
影响因子：
2.9
作者：
Wang, Cheng;Shan, Ying;Xu, Wei
通讯作者：
Xu, Wei
DOI：
10.1073/pnas.0700499104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Leuenroth, Stephanie J.;Okuhara, Dayne;Crews, Craig M.
通讯作者：
Crews, Craig M.