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REVIEW article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1397441
This article is part of the Research Topic Inflammatory responses on the road from NASH to HCC: pathogenic mechanisms and possible therapeutic strategies View all 7 articles

Protease Activated Receptor 2 as a novel druggable target for the treatment of metabolic dysfunction-associated fatty liver disease and cancer

Provisionally accepted
Gianmarco Villano Gianmarco Villano Patrizia Pontisso Patrizia Pontisso *
  • University of Padua, Padua, Italy

The final, formatted version of the article will be published soon.

    Metabolic dysfunction-associated fatty liver disease (MAFLD) is spreading worldwide, largely due to unhealthy lifestyles that contribute to the rise in diabetes, metabolic syndrome, and obesity. In this situation, the progression of injury to metabolic steatohepatitis can evolve to cirrhosis and, eventually, to hepatocellular carcinoma (HCC).It is well known that serine protease enzymes with different functions in cellular homeostasis, act as signaling molecules that regulate liver inflammation by activating the Protease-Activated Receptors (PARs) family members, expressed on the cellular plasma membrane. Among them, PAR2 plays a central role in the activation of signaling pathways in response to changes in the extracellular microenvironment. Experimental data have provided evidence that PAR2 is involved not only in the inflammatory response, but also in insulin resistance, lipid metabolism and cancer.The major aims of this narrative review are addressed to assess PAR2 involvement in inflammation, metabolism and liver disease progression and to explore possible therapeutic strategies, based on PAR2 inhibition, in order to prevent its biological effects in the context of MAFLD and cancer.

    Keywords: PAR2, Proteases, metabolic dysfunction, Fatty liver disease, PAR2 inhibition

    Received: 07 Mar 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Villano and Pontisso. 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) or licensor 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: Patrizia Pontisso, University of Padua, Padua, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.