PAR2 regulates regeneration, transdifferentiation, and death

Ron Piran, Seung Hee Lee, Pia Kuss, Ergeng Hao, Robbin Newlin, José Luis Millán, Fred Levine

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Understanding the mechanisms by which cells sense and respond to injury is central to developing therapies to enhance tissue regeneration. Previously, we showed that pancreatic injury consisting of acinar cell damage+β-cell ablation led to islet cell transdifferentiation. Here, we report that the molecular mechanism for this requires activating protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2 modulation was sufficient to induce islet cell transdifferentiation in the absence of β-cells. Its expression was modulated in an islet cell type-specific manner in murine and human type 1 diabetes (T1D). In addition to transdifferentiation, PAR2 regulated β-cell apoptosis in pancreatitis. PAR2’s role in regeneration is broad, as mice lacking PAR2 had marked phenotypes in response to injury in the liver and in digit regeneration following amputation. These studies provide a pharmacologically relevant target to induce tissue regeneration in a number of diseases, including T1D.

Original languageEnglish
Article numbere2452
JournalCell Death and Disease
Volume7
Issue number11
DOIs
StatePublished - 3 Nov 2016

Bibliographical note

Publisher Copyright:
© The Author(s) 2016.

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