MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury

Huaxun Wu; Hui Li; Wen Wen; Yongchao Wang; Hong Xu; Mei Xu; Jacqueline A Frank; Wei Wei; Jia Luo

doi:10.1002/jhbp.928

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MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury

Journal article

Peer reviewed

MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury

Huaxun Wu, Hui Li, Wen Wen, Yongchao Wang, Hong Xu, Mei Xu, Jacqueline A Frank, Wei Wei and Jia Luo

Journal of hepato-biliary-pancreatic sciences, Vol.28(10), pp.883-892

02/28/2021

DOI: 10.1002/jhbp.928

PMCID: PMC8397795

PMID: 33644980

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https://www.ncbi.nlm.nih.gov/pmc/articles/8397795View

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Abstract

Heavy alcohol drinking is associated with pancreatitis. Pancreatitis is initiated by the damage to the pancreatic acinar cells. The endoplasmic reticulum (ER) stress has been shown to play an important role in alcohol-induced pancreatic damage. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible protein. The aim of the study was to determine whether MANF can ameliorate alcohol-induced ER stress and cellular damages to pancreatic acinar cells. Alcohol-induced damage to mouse pancreatic 266-6 acinar cells was determined by MTT and flow cytometry. MANF expression was downregulated by MANF siRNA using the Neon Transfection System. The overexpression of MANF was performed by the infection with the adenoviral vector carrying mouse MANF gene. The expression of ER stress markers was determined by immunoblotting and immunofluorescence. Alcohol caused ER stress, oxidative stress and induced apoptosis of 266-6 acinar cells. Recombinant human MANF alleviated alcohol-induced ER stress and cell death by inhibiting IRE1-caspase 12-caspase 3 apoptotic pathway. Overexpression of mouse MANF also protected cells against alcohol-induced apoptosis. In contrast, inhibiting MANF by siRNA exacerbated alcohol-induced cellular damage. MANF was protective against alcohol-induced ER stress and cellular injury in pancreatic acinar cells. The findings suggest a potential therapeutic value of MANF for alcoholic pancreatitis.

Apoptosis

Oxidative Stress

unfolded protein response

pancreatitis

Alcohol abuse

endoplasmic reticulum stress

Details

Title: Subtitle: MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury
Creators: Huaxun Wu - Anhui Medical University
Hui Li - University of Iowa
Wen Wen - University of Iowa
Yongchao Wang - Vanderbilt University
Hong Xu - University of Kentucky
Mei Xu - University of Kentucky
Jacqueline A Frank - University of Kentucky
Wei Wei - Anhui Medical University
Jia Luo - University of Iowa
Resource Type: Journal article
Publication Details: Journal of hepato-biliary-pancreatic sciences, Vol.28(10), pp.883-892
DOI: 10.1002/jhbp.928
PMID: 33644980
PMCID: PMC8397795
NLM abbreviation: J Hepatobiliary Pancreat Sci
ISSN: 1868-6974
eISSN: 1868-6982
Grant note: gxyqZD2018023 / Key Project of Anhui province university outstanding youth talent fund AA015407 / National Institutes of Health AA017226 / National Institutes of Health BX001721 / Biomedical Laboratory Research and Development, VA Office of Research and Development
Language: English
Date published: 02/28/2021
Academic Unit: Pathology
Record Identifier: 9984186390702771

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