MANF Protects Pancreatic Acinar Cells

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 alcoholâ€induced pancreatic damage. Mesencephalic astrocyteâ€derived neurotrophic factor (MANF) is an ER stressâ€inducible protein. The aim of the study was to determine whether MANF can ameliorate alcoholâ€induced ER stress and cellular damages to pancreatic acinar cells. Alcoholâ€induced damage to mouse pancreatic 266â€6 acinar cells was determined by MTT and flow cytometry. MANF expression was downâ€regulated by MANF siRNA using a Neon Transfection System. The overâ€expression 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 266â€6 acinar cells. Recombinant human MANF alleviated alcoholâ€induced ER stress and cell death by inhibiting IRE1â€caspase 12â€caspase 3 apoptotic pathway. Overexpression of mouse MANF also protected cells against alcoholâ€induced apoptosis. In contrast, inhibiting MANF by siRNA exacerbated alcoholâ€induced cellular damage. MANF was protective against alcoholâ€induced ER stress and cellular injury in pancreatic acinar cells. The findings suggest a potential therapeutic value of MANF for alcoholic pancreatitis. More details-https://onlinelibrary.wiley.com/doi/abs/10.1002/jhbp.928 Pancreatic disorders and Therapy is now accepting submissions on this topic. A standard EDITORIAL TRACKING SYSTEM is utilized for manuscript submission, review, editorial processing and tracking which can be securely accessed by the authors, reviewers and editors for monitoring and tracking the article processing. Manuscripts can be uploaded online at Editorial Tracking System (www.longdom.org/submissions/pancreatic-disorders-therapy.html ) or forwarded to the Editorial Office at manuscripts@longdom.org
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Pancreatic disorders and Therapy