Reg4 regulates pancreatic regeneration following pancreatitis via modulating the Notch signaling

J Cell Physiol. 2021 Nov;236(11):7565-7577. doi: 10.1002/jcp.30397. Epub 2021 Apr 26.

Abstract

Pancreatic regeneration after acute pancreatitis is critical in the normal restoration of pancreatic exocrine function, the inhibition of which can cause severe complications including pancreatic exocrine insufficiency. However, the regulators of pancreatic regeneration and the underlying mechanisms remain uncovered. Here, using the inducible Tet-on system, we found that regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration after pancreatitis. Both acinar-to-ductal metaplasia and the resolution of pancreatitis during regeneration were affected by Reg4 knockdown. Further investigations confirmed that Reg4 exerted its function through regulating Notch activation both in vitro and in vivo. Our study revealed Reg4 as a new regulator and potential therapeutic target for pancreatic regeneration.

Keywords: ADM; Notch; Reg4; cell proliferation; pancreatic regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Disease Models, Animal
  • HEK293 Cells
  • Humans
  • Male
  • Metaplasia
  • Mice
  • Mice, Inbred C57BL
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatitis / genetics
  • Pancreatitis / metabolism*
  • Pancreatitis / pathology
  • Pancreatitis-Associated Proteins / metabolism*
  • Receptors, Notch / metabolism*
  • Regeneration*
  • Signal Transduction

Substances

  • Pancreatitis-Associated Proteins
  • REG4 protein, mouse
  • Receptors, Notch