Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Sep 29, 2018; 9(2): 37-46
Published online Sep 29, 2018. doi: 10.4291/wjgp.v9.i2.37
Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis
Kaylene Barrera, Albert Stanek, Kei Okochi, Zuzanna Niewiadomska, Cathy Mueller, Peiqi Ou, Devon John, Antonio E Alfonso, Scott Tenner, Chongmin Huan
Kaylene Barrera, Zuzanna Niewiadomska, Cathy Mueller, Devon John, Antonio E Alfonso, Department of Surgery, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States
Albert Stanek, Department of Surgery and Pathology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States
Kei Okochi, College of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States
Peiqi Ou, School of Graduate Studies, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States
Scott Tenner, Greater New York Endoscopy Surgical Center, State University of New York, Brooklyn, NY 11235, United States
Chongmin Huan, Department of Surgery and Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States
Author contributions: Barrera K, Stanek A, Tenner S and Huan C conceptualized, designed and drafted the study; Barrera K, Stanek A, Okochi K, Niewiadomska Z, Tenner S and Huan C reviewed literatures; Barrera K, Stanek A, Mueller C, Ou P, John D, Alfonso AE, Tenner S and Huan C revised and edited the manuscript.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Chongmin Huan, MD, PhD, Assistant Professor, Department of Surgery and Cell Biology, State University of New York, Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, United States. chongmin.huan@downstate.edu
Telephone: +1-718-2706772 Fax: +1-718-2216132
Received: June 21, 2018
Peer-review started: June 21, 2018
First decision: July 23, 2018
Revised: July 24, 2018
Accepted: August 21, 2018
Article in press: August 21, 2018
Published online: September 29, 2018
Processing time: 99 Days and 11.1 Hours
Abstract

Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR’s signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB’s pro-inflammatory activity and impair autophagy’s protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.

Keywords: Acute pancreatitis; Endoplasmic reticulum stress; Unfolded protein response; Acinar cell injury; Autophagy

Core tip: The widely-accepted autodigestion theory of acute pancreatitis (AP) has been considerably modified by the recent recognition of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) as an essential self-protective activity in acinar cells. Inadequate UPR, however, leads to acinar cell injury in AP with elusive mechanisms. We review the relevant literature and propose mechanistic models with the hope of facilitating the research required for the development of effective AP treatment.