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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Vydané v:Cellular and molecular gastroenterology and hepatology Ročník 17; číslo 4; s. 639 - 656
Hlavní autori: 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:English
Vydavateľské údaje: United States Elsevier Inc 2024
Predmet:
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]
Bibliografia: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