Distinct extracellular-matrix remodeling events precede symptoms of inflammation

Elee Shimshoni, Idan Adir, Ran Afik, Inna Solomonov, Anjana Shenoy, Miri Adler, Luca Puricelli, Fabio Mira Rocha Sabino, Simonas Savickas, Odelia Mouhadeb, Nathan Gluck, Sigal Fishman, Lael Werner, Tomer-Meir Salame, Dror S. Shouval, Chen Varol, Ulrich auf dem Keller, Alessandro Podestà, Tamar Geiger, Paolo MilaniUri Alon, Irit Sagi*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalMatrix Biology
Volume96
Pages (from-to)47-68
Number of pages22
ISSN0945-053X
DOIs
Publication statusPublished - 2021

Keywords

  • Extracellular matrix
  • Proteomics
  • Electron microscopy
  • Proteolysis
  • Inflammation
  • Colitis

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