Curcumin Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway.
Curcumin has exhibited a protective effect against development of renal fibrosis in animal models, however, its underlying molecular mechanisms are largely unclear. Therefore, we investigated the anti-fibrosis effects of curcumin in transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-β1 or curcumin alone, or TGF-β1 in combination with curcumin. The effect of curcumin on cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of E-cadherin, cytokeratin, vimentin, alpha smooth muscle actin (α-SMA), fibroblast-specific protein 1 (FSP1) and key proteins of Akt/mammalian target of rapamycin (mTOR) pathway were analyzed by immunocytochemistry, real-time PCR and Western blot. Low dose curcumin (3.125 and 25 µmol/L) effectively promoted HKC proliferation. When HKCs were co-incubated with TGF-β1 and curcumin for 72 h, curcumin maintained the epithelial morphology in a dose-dependent manner, decreased expression of vimentin, α-SMA and FSP1 normally induced by TGF-β1, and increased expression of E-cadherin, cytokeratin. Importantly, we found that curcumin reduced Akt, mTOR and P70S6K phosphorylation, effectively suppressing the activity of the Akt/mTOR pathway in HKCs. Curcumin also promoted HKC proliferation, and antagonized TGF-β1-driven EMT through the inhibition of Akt/mTOR pathway activity, which may suggest an alternative therapy for renal fibrosis.
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University.
Fang-Qiang
FQ
Zhu
Min-Jia
MJ
Chen
Ming
M
Zhu
Rong-Seng
RS
Zhao
Wei
W
Qiu
Xiang
X
Xu
Hong
H
Liu
Hong-Wen
HW
Zhao
Rong-Jie
RJ
Yu
Xiong-Fei
XF
Wu
Keqin
K
Zhang
Hong
H
Huang
D000199:Actins / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002135:Calcium-Binding Proteins; D000071999:S100 Calcium-Binding Protein A4; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C077591:S100A4 protein, human; D007633:Keratins; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin