Journal article
Distinct extracellular-matrix remodeling events precede symptoms of inflammation
Weizmann Institute of Science1
Tel Aviv University2
Universitá degli Studi di Milano3
Department of Biotechnology and Biomedicine, Technical University of Denmark4
DTU Proteomics Core, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark5
Protease Network Degradomics, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark6
Tel Aviv Sourasky Medical Center7
Sheba Medical Center8
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.
Language: | English |
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Year: | 2021 |
Pages: | 47-68 |
ISSN: | 15691802 and 0945053x |
Types: | Journal article |
DOI: | 10.1016/j.matbio.2020.11.001 |
ORCIDs: | 0000-0003-3057-5393 , 0000-0003-2486-1350 , 0000-0001-5279-9211 , 0000-0003-4966-410X , 0000-0002-4169-6679 , Sabino, Fabio Mira Rocha and auf dem Keller, Ulrich |