PSTPIP2 protects against alcoholic liver injury and invokes STAT3-mediated suppression of apoptosis.

Autor: Yin NN; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China; Department of Pharmacology, The Traditional Chinese Medicine Hospital of Huoshan County, Luan 237200, Anhui, China., Chen X; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China., Sun YY; Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China., Yang L; Department of Pharmacology, The Second Hospital of Anhui Medical University, 678 Furong Road, Hefei 230601, Anhui, China., Zhang YF; Department of Pharmacology, The Second Hospital of Anhui Medical University, 678 Furong Road, Hefei 230601, Anhui, China., Niu XN; Department of Pharmacology, Infection Hospital of Anhui Provincial Hospital, Hefei Infectious Disease Hospital, Hefei 230601, Anhui, China., Song H; Office of Huoshan Vocational School, Luan 237200, Anhui, China., Huang C; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China., Li J; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Jul; Vol. 225, pp. 116334. Date of Electronic Publication: 2024 May 31.
DOI: 10.1016/j.bcp.2024.116334
Abstrakt: Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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