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Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00235

Four Decades After The Discovery Of Regenerating Islet-Derived (Reg) Proteins: Current Understanding and Challenges

 Zijing Chen1, Shawna Downing1 and  Emmanuel S. Tzanakakis1, 2*
  • 1Tufts University, United States
  • 2Tufts Medical Center, United States

Regenerating islet-derived (Reg) proteins have emerged as multifunctional agents with pro-proliferative, anti-apoptotic, differentiation-inducing and bactericidal properties. Over the last forty years since first discovered, Reg proteins have been implicated in a gamut of maladies including diabetes, various types of cancer of the digestive tract, and Alzheimer disease. Surprisingly though, a consensus is still absent on the regulation of their expression, and molecular underpinning of their function. Here, we provide a critical appraisal of recent findings in the field of Reg protein biology. Specifically, the structural characteristics are reviewed particularly in connection with established or purported functions of different members of the Reg family. Moreover, Reg expression patterns in different tissues both under normal and pathophysiological conditions are summarized. Putative receptors and cascades reported to relay Reg signaling inciting cellular responses are presented aiming at a better appreciation of the biological activities of the distinct Reg moieties. Challenges are also discussed that have hampered thus far the rapid progress in this field such as the use of non-standard nomenclature for Reg molecules among various research groups, the existence of multiple Reg members with significant degree of homology and possibly compensatory modes of action, and the need for common assays with robust readouts of Reg activity. Coordinated research is warranted going forward, given that several research groups have independently linked Reg proteins to diseased states and raised the possibility that these biomolecules can serve as therapeutic targets and biomarkers.

Keywords: Reg proteins, Pancreas, diabetes, Pancreatic adenocarcinoma, gastrointenstinal cancer, Pancreatitis

Received: 19 Jul 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Chen, Downing and Tzanakakis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Emmanuel S. Tzanakakis, Tufts University, Medford, 02155, Massachusetts, United States,