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Distinct extracellular–matrix remodeling events precede symptoms of inflammation

Authors :
Fabio Sabino
Dror S. Shouval
Irit Sagi
Inna Solomonov
Sigal Fishman
Chen Varol
Odelia Mouhadeb
Tamar Geiger
Elee Shimshoni
Simonas Savickas
Lael Werner
Idan Adir
Tomer-Meir Salame
Uri Alon
Miri Adler
Luca Puricelli
Paolo Milani
Ulrich auf dem Keller
Ran Afik
Nathan Gluck
Anjana Shenoy
Alessandro Podestà
Source :
Shimshoni, E, Adir, I, Afik, R, Solomonov, I, Shenoy, A, Adler, M, Puricelli, L, Sabino, F M R, Savickas, S, Mouhadeb, O, Gluck, N, Fishman, S, Werner, L, Salame, T-M, Shouval, D S, Varol, C, auf dem Keller, U, Podestà, A, Geiger, T, Milani, P, Alon, U & Sagi, I 2021, ' Distinct extracellular-matrix remodeling events precede symptoms of inflammation ', Matrix Biology, vol. 96, pp. 47-68 . https://doi.org/10.1016/j.matbio.2020.11.001, Matrix Biology

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.

Details

Language :
English
ISSN :
0945053X
Volume :
96
Database :
OpenAIRE
Journal :
Matrix Biology
Accession number :
edsair.doi.dedup.....c3cee40f005ca1cacc9816b0b8414426
Full Text :
https://doi.org/10.1016/j.matbio.2020.11.001