Distinct extracellular-matrix remodeling events precede symptoms of inflammation

Identification of early processes leading to complex tissue pathologies, such as inflammatory bowel diseases, poses a major scientific and clinical challenge that is imperative for improved diagnosis and treatment. Most studies of inflammation onset focus on cellular processes and signaling molecules, while overlooking the environment in which they take place, the continuously remodeled extracellular matrix. In this study, we used colitis models for investigating extracellular-matrix dynamics during disease onset, while treating the matrix as a complete and defined entity. Through the analysis of matrix structure, stiffness and composition, we unexpectedly revealed that even prior to the first clinical symptoms, the colon displays its own unique extracellular-matrix signature and found specific markers of clinical potential, which were also validated in human subjects. We also show that the emergence of this pre-symptomatic matrix is mediated by subclinical infiltration of immune cells bearing remodeling enzymes. Remarkably, whether the inflammation is chronic or acute, its matrix signature converges at pre-symptomatic states. We suggest that the existence of a pre-symptomatic extracellular-matrix is general and relevant to a wide range of diseases. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

This study investigates the extracellular-matrix dynamics during the onset of inflammatory bowel diseases, revealing a unique matrix signature in the colon even before the appearance of clinical symptoms. The presence of a pre-symptomatic matrix mediated by immune cells carrying remodeling enzymes was found, suggesting its relevance to a wide range of diseases, both chronic and acute.