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World J Gastroenterol. Nov 21, 2014; 20(43): 16146-16152
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16146
Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis
Jun Li, Rui Zhou, Jian Zhang, Zong-Fang Li
Jun Li, National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, the Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an 710004, Shaanxi Province, China
Rui Zhou, Jian Zhang, Zong-Fang Li, Department of General Surgery, National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, the Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an 710004, Shaanxi Province, China
Author contributions: Li J and Zhou R collected the underlying material and wrote the initial draft of the manuscript; Li J, Zhou R, Zhang J and Li ZF designed the outline of the paper; Li ZF finalized and revised the manuscript; all authors read and approved the final version of the manuscript.
Supported by grants from the National Natural Science Foundation of China No. 30171167, No. 30901945 and the Specialized Research Fund for the Doctoral Program of Higher Education No. 20130201130009
Correspondence to: Zong-Fang Li, MD, PhD, Department of General Surgery, National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine, No. 157 West 5th Road, Xi’an 710004, Shaanxi Province, China. lzf2568@gmail.com
Telephone: +86-29-87678006 Fax: +86-29-87678634
Received: February 28, 2014
Revised: June 9, 2014
Accepted: July 11, 2014
Published online: November 21, 2014
Processing time: 265 Days and 9.1 Hours
Abstract

Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca2+) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca2+ overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca2+ signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca2+ elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca2+ from stores in the intracellular endoplasmic reticulum and/or increased Ca2+ entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca2+ by the sarco/endoplasmic reticulum Ca2+-activated ATPase and plasma membrane Ca2+-ATPase pumps, which contribute to Ca2+ overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca2+ signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca2+ signals in the pathogenesis of pancreatitis.

Keywords: Pancreatitis; Calcium signaling; Pancreatic acinar cells; Overload; Cell injury

Core tip: Calcium (Ca2+) overload is crucial in the pathogenesis of pancreatitis, which results in trypsin activation, vacuolization and necrosis. Such cell injury results from increased Ca2+ released from intracellular endoplasmic reticulum Ca2+ stores, increased Ca2+ entry through the plasma membrane and Ca2+ pump defects. Current findings have provided further insight into the roles and mechanisms of Ca2+ overload in pancreatitis. The lack of specific treatments is a stimulus for ongoing research. This review summarizes recent advances in our understanding of Ca2+ signaling in the pathogenesis of pancreatitis, and discusses how research has guided our search for potential therapeutic targets.