Format

Send to

Choose Destination
Cell Cycle. 2019 Sep;18(18):2239-2254. doi: 10.1080/15384101.2019.1642067. Epub 2019 Aug 5.

Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway.

Author information

1
Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital, Southern Medical University , Guangzhou , P. R. China.
2
Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University , Guangzhou , P. R. China.

Abstract

Alcoholic hepatitis (AH) is a severe condition developed in patients with underlying alcoholic liver disease. Epithelial cell adhesion molecule (EPCAM) plays a role in hepatitis. Therefore, the current study aimed to explore the effect of EPCAM and its potential mechanism in AH. Bioinformatic analysis was performed to screen differentially expressed genes associated with AH. AH mouse models were established through a Lieber-DeCarli liquid diet containing 4% ethanol, which were co-treated with siRNA against EPCAM or the PI3K/Akt/mTOR signaling pathway inhibitor in order to investigate the effects of EPCAM and the PI3K/Akt/mTOR signaling pathway on hepatic fibrosis, hepatic stellate cell (HSC) proliferation and apoptosis. The relationship between EPCAM and the PI3K/Akt/mTOR signaling pathway was investigated for the purposes of elucidating the potential mechanism of EPCAM in AH. EPCAM was predicted to regulate AH progression through the PI3K/Akt/mTOR signaling pathway. Silencing EPCAM or inhibition of the PI3K/Akt/mTOR signaling pathway inhibited the hepatic fibrosis and HSC proliferation yet induced HSC apoptosis. Moreover, silencing EPCAM was found to repress the PI3K/Akt/mTOR signaling pathway as evidenced by decreased levels of Bcl2 yet increased levels of caspase-3. Collectively, silencing EPCAM could hinder AH progression by inhibiting the PI3K/Akt/mTOR signaling pathway, which might serve as a potential therapeutic target for AH treatment.

KEYWORDS:

Epithelial cell adhesion molecule; PI3K/Akt/mTOR signaling pathway; alcoholic hepatitis; hepatic fibrosis; hepatic stellate cell; proliferation and apoptosis

PMID:
31378124
PMCID:
PMC6738525
[Available on 2020-08-05]
DOI:
10.1080/15384101.2019.1642067

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center