Studies on the mechanism of SIRT1/AMPK signaling pathway between hepatocytes and hepatic stellate cells

Ting BAI,Yong YANG,Ji-xing NAN,Qing-gao ZHANG

(1.Medical College of Dalian University,Dalian 116622,China;2.Key Laboratory for Natural Resource of Changbai Mountain&Functional Molecules,Ministry of Education,College of Pharmacy,Yanbian University,Yanji 133002,China）

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Studies on the mechanism of SIRT1/AMPK signaling pathway between hepatocytes and hepatic stellate cells

Ting BAI1,Yong YANG1,Ji-xing NAN2,Qing-gao ZHANG1

(1.Medical College of Dalian University,Dalian 116622,China;2.Key Laboratory for Natural Resource of Changbai Mountain&Functional Molecules,Ministry of Education,College of Pharmacy,Yanbian University,Yanji 133002,China）

OBJECTIVETo investigate the mechanism of SIRT1/AMPK signaling pathway between hepatocytes and hepatic stellate cells(HSCs).METHODSNormal human Chang liver cells and human hepatic stellate cell line,LX-2 cells were treated with SRT1720(10 μmol·L-1)and AICAR(500 μmol·L-1)prior to ethanol(50 mmol·L-1)for 24 and 48 h.Cell viability was analyzed by methyl thiazolyl tetrazolium assay.SIRT1,AMPK and p-AMPK mRNA levels for 24 h and 48 h were analyzed by RT-PCR,SIRT1,AMPK and p-AMPK protein expressions in the supernatant at 24 and 48 h was detected by Western blot.RESULTSSRT1720 and AICAR effectively decreased LX-2 cell viabilities and exhibited scarcely little toxicity in human Chang liver cells.SRT1720 and AICAR attenuated collagen-I,α-smooth muscle actin(α-SMA)levels,activated liver kinase B-1(LKB1)and AMPK phosphorylation in ethanol treated LX-2 cells.Meanwhile,SRT1720 and AICAR enhanced SIRT1 expression mediated by ethanol both in Chang liver cells and LX-2 cells.Furthermore,SRT1720 and AICAR suppressed the expression of sterol regulatory element-binding protein-1(SREBP-1)to regulate fatty acid synthesis.CONCLUSIONSIRT1 agonist and AMPK agonist blocked the crosstalk between hepatocytes and HSCs via SIRT1/AMPK signaling pathway to modulate hepatocytes accumulation of lipid and HSCs activation.

hepatic stellate cells;hepatocytes;SIRT1;AMPK

The project supported by National Natural Science Foundation of China(81700523)

Qing-gao ZHANG,Tel:(0411)87402916,E-mail：zhangqinggao@dlu.edu.cn