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Distinct extracellular-matrix remodeling events precede symptoms of inflammation.
- Source :
-
Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2021 Feb; Vol. 96, pp. 47-68. Date of Electronic Publication: 2020 Nov 25. - Publication Year :
- 2021
-
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.<br />Competing Interests: Declaration of Competing Interest The authors declare no competing interests.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Case-Control Studies
Colitis, Ulcerative chemically induced
Colitis, Ulcerative genetics
Colitis, Ulcerative metabolism
Dextran Sulfate adverse effects
Disease Models, Animal
Extracellular Matrix metabolism
Extracellular Matrix ultrastructure
Female
Gene Knockdown Techniques
Humans
Machine Learning
Male
Mice
Piroxicam adverse effects
Prognosis
Proteomics
Biomarkers metabolism
Colitis, Ulcerative pathology
Extracellular Matrix pathology
Interleukin-10 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1569-1802
- Volume :
- 96
- Database :
- MEDLINE
- Journal :
- Matrix biology : journal of the International Society for Matrix Biology
- Publication Type :
- Academic Journal
- Accession number :
- 33246101
- Full Text :
- https://doi.org/10.1016/j.matbio.2020.11.001