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 knockout () 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.

中文翻译：

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慢性炎症小鼠结肠组织重塑的细胞外基质编排

慢性炎症性疾病是一种使人衰弱且反复发作的疾病，与严重的合并症相关，包括患癌症的风险增加。广泛的组织重塑是此类疾病的标志，并且既是疾病进展的结果，也是疾病进展的介质。尽管先前对炎症性肠病期间上皮和间质重塑的特征进行了描述，但仍缺乏对其对疾病进展影响的完整了解。使用数据独立采集的综合蛋白质组学流程应用于来自结肠炎敲除小鼠模型的脱细胞结肠样本，以深入表征细胞外基质重塑。从病理前和明显的结肠炎中提取了基质体景观的独特蛋白质组谱。从同一小鼠模型中提取的蛋白质组学和转录组学数据集的整合产生了网络图，描述了基质体蛋白在结肠炎进展过程中组织重塑中的协调作用。这里使用的深入蛋白质组工作流程允许将 34 种蛋白质添加到已知的结肠基质体特征中。提取病理前和病理性结肠炎状态的蛋白质特征，通过富含亮氨酸的小蛋白聚糖的表达来区分这两种状态。我们概述了此类蛋白和其他基质体蛋白在结肠炎期间组织重塑中的作用，以及基质体配体协调调节细胞类型的潜力。我们的工作强调了基质体蛋白在结肠炎期间组织重塑中的核心作用，并定义了可用于选择治疗靶点的编排节点。