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2000
Volume 25, Issue 7
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Aims

To clarify the roles of PAR-2 (protease-activated receptor 2) in Crohn's disease-associated colonic fibrosis.

Background

G protein-coupled receptor, termed PAR-2, is triggered after serine proteases. Through activating genes encoding extracellular matrix proteins and proinflammatory cytokines, PAR-2 triggering promotes inflammatory / pro-fibrotic pathways. Although PAR-2 is highly expressed within the digestive system, its significance within colonic fibrosis (CF) has not yet been probed.

Objective

To assess the roles and mechanisms of PAR-2 in Crohn's disease-associated colonic fibrosis.

Methods

PAR-2 expression was assessed variably in the colon of human and model mice. Immunofluorescence assay was used to analyze the phenotypic changes of fibroblasts after PAR-2 activation in the lamina propria. In assays, we explored the roles of PAR-2 in CCD-18Co fibroblasts treated with PAR-2 inhibitor ENMD-1068 and PAR-2 agonist SLIGRL-NH2.

Results

PAR-2 was highly expressed in the subepithelial layer surrounding colonic crypts of CD patients or murine fibrosis cohort. Colonic PAR-2 expression was consistent with collagen deposition. Decreasing PAR-2 in experimental colon fibrosis caused a decrease in the amount of colonic collagen and histological fibrosis, followed by a reduction in colonic fibroblast activation. PAR-2 activation enhanced CF by showing a profibrogenic phenotype and collagen synthesis within CCD-18Co fibroblasts.

Conclusion

Our results show that PAR-2 activation could upregulate extracellular matrix (ECM) proteomic levels, encourage CF, and cause a pro-fibrogenic phenotype within human colonic myofibroblasts.

© 2025 Bentham Science Publishers
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2025-10-27

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Protease-activated Receptor 2 Promotes Crohn's Disease-Associated Colonic Fibrosis through Fibroblast Activation
Current Molecular Medicine 25, 916 (2025); https://doi.org/10.2174/0115665240351860250403112214
/content/journals/cmm/10.2174/0115665240351860250403112214
/content/journals/cmm/10.2174/0115665240351860250403112214
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  • Article Type:     Research Article
Keyword(s): colonic fibrosis; Crohn's disease; fibroblast; myofibroblast; PAR-2

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