Extracellular Matrix Orchestration of Tissue Remodeling in the Chronically Inflamed Mouse Colon

Chronic inflammatory illnesses are debilitating and recurrent conditions associated with significant comorbidities, including an increased risk of developing cancer. Extensive tissue remodeling is a hallmark of such illnesses, and is both a consequence and a mediator of disease progression. Despite...

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Vydáno v:	Cellular and molecular gastroenterology and hepatology Ročník 17; číslo 4; s. 639 - 656
Hlavní autoři:	Moutin, Elisa B., Bons, Joanna, Giavara, Giada, Lourenco, Filipe, Pan, Deng, Burton, Jordan B., Shah, Samah, Colombé, Mathilde, Gascard, Philippe, Tlsty, Thea, Schilling, Birgit, Winton, Douglas J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 2024
Témata:	Animals Cell-Matrix Interactions Chronic Disease Colitis - pathology DIA Proteomics Disease Progression Extracellular Matrix - metabolism Gastroenterology and Hepatology Inflammatory Bowel Disease Mice Proteoglycans Proteomics DIA Proteomics Proteoglycans Grem1 SDS DTT MS iRT It ACN ECM UC Serpin H1 SLRP TEAB Cell-Matrix Interactions TGF-β Lamc1 Inflammatory Bowel Disease FA DIA triethylammonium bicarbonate Integrin mass spectrometry sodium dodecyl sulfate acetonitrile ulcerative colitis formic acid dithiothreitol Laminin subunit gamma 1 data-independent acquisition indexed retention time transforming growth factor-β Gremlin 1 small leucine-rich proteoglycan extracellular matrix Serpin family H member 1
ISSN:	2352-345X, 2352-345X
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Shrnutí:	Chronic inflammatory illnesses are debilitating and recurrent conditions associated with significant comorbidities, including an increased risk of developing cancer. Extensive tissue remodeling is a hallmark of such illnesses, and is both a consequence and a mediator of disease progression. Despite previous characterization of epithelial and stromal remodeling during inflammatory bowel disease, a complete understanding of its impact on disease progression is lacking. A comprehensive proteomic pipeline using data-independent acquisition was applied to decellularized colon samples from the Muc2 knockout (Muc2KO) mouse model of colitis for an in-depth characterization of extracellular matrix remodeling. Unique proteomic profiles of the matrisomal landscape were extracted from prepathologic and overt colitis. Integration of proteomics and transcriptomics data sets extracted from the same murine model produced network maps describing the orchestrating role of matrisomal proteins in tissue remodeling during the progression of colitis. The in-depth proteomic workflow used here allowed the addition of 34 proteins to the known colon matrisomal signature. Protein signatures of prepathologic and pathologic colitic states were extracted, differentiating the 2 states by expression of small leucine-rich proteoglycans. We outlined the role of this class and other matrisomal proteins in tissue remodeling during colitis, as well as the potential for coordinated regulation of cell types by matrisomal ligands. Our work highlights a central role for matrisomal proteins in tissue remodeling during colitis and defines orchestrating nodes that can be exploited in the selection of therapeutic targets. [Display omitted]
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2352-345X 2352-345X
DOI:	10.1016/j.jcmgh.2024.01.003