PTTG1 alleviates acute alcoholic liver injury by inhibiting endoplasmic reticulum stress-induced hepatocyte pyroptosis
Shiuan Tien
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorHaoxiong Zhou
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorQi Zhou
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorHuiling Liu
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorBin Wu
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorCorresponding Author
Yunwei Guo
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Correspondence
Yunwei Guo, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, 510630 Guangzhou, China.
Email: [email protected]
Search for more papers by this authorShiuan Tien
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorHaoxiong Zhou
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorQi Zhou
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorHuiling Liu
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorBin Wu
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Search for more papers by this authorCorresponding Author
Yunwei Guo
Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
Correspondence
Yunwei Guo, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, 510630 Guangzhou, China.
Email: [email protected]
Search for more papers by this authorShiuan Tien and Haoxiong Zhou contributed equally.
Handling Editor: Dr. Luca Valenti
Abstract
Background & Aims
Heavy drinking is a primary cause of alcoholic liver injury (ALI). Pituitary tumour transforming gene 1 (PTTG1) is involved in the occurrence and development of hepatocellular carcinoma (HCC), which is a well-known inflammation-related cancer with various aetiologies, including alcohol consumption. However, the role of PTTG1 in alcohol-induced liver injury and inflammation is not clear.
Methods
Blood samples were collected from patients with acute alcohol intoxication (n = 20) and healthy controls (n = 20). PTTG1 knockout (KO) mice and PTTG1 transgenic (TG) mice were given a single gavage of alcohol (5 g/kg, 50%) to construct the alcohol-induced liver injury.
Results
We found that serum PTTG1 levels were downregulated in acute ALI patients. In addition, acute alcohol administration significantly reduced PTTG1 levels in the serum and liver of mice. Compared to wild-type mice, PTTG1 KO mice had more serious liver injury, which was accompanied by worsened hepatic endoplasmic reticulum (ER) stress and hepatocyte pyroptosis induced by alcohol. Similarly, PTTG1 deficiency exacerbated alcohol-induced cell death in primary mouse hepatocytes and LO2 cells, by increasing hepatic ER stress and pyroptosis. Importantly, TUDCA, an ER stress inhibitor, could blocked alcohol-induced hepatic pyroptosis in PTTG1 knockdown LO2 cells. Finally, overexpression of PTTG1 substantially attenuated alcohol-induced liver injury by reducing ER stress and hepatic pyroptosis in mice.
Conclusions
We demonstrated that PTTG1 participates in ALI and has a protective effect against alcohol-induced hepatic ER stress and pyroptosis.
CONFLICT OF INTEREST STATEMENT
No other authors have competing interests to declare.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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