The hepatic "matrisome" responds dynamically to injury: Characterization of transitional changes to the extracellular matrix in mice.
The hepatic "matrisome" responds dynamically to injury: Characterization of transitional changes to the extracellular matrix in mice.
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DOI：
10.1002/hep.28918
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Arteel GE
中科院分区：
文献类型：
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作者：
Massey VL;Dolin CE;Poole LG;Hudson SV;Siow DL;Brock GN;Merchant ML;Wilkey DW;Arteel GE
细胞外基质（ECM）由多种成分组成，这些成分与周围细胞双向作用，以产生反应性微环境。在某些情况下（例如，肝纤维化），ECM的变化是公认和理解的。然而，越来越多的人接受肝ECM蛋白质组（即，基质体）在纤维化之前很好地动态响应应激。术语“移行组织重塑”描述了响应于损伤的定性和定量ECM变化，其不改变器官的整体结构; ECM的这些变化可能有助于早期疾病的开始和/或进展。对肝损伤中ECM的这些变化的性质和程度知之甚少。这项工作的目的是验证ECM蛋白质组的分析，并比较6周乙醇饮食和/或急性脂多糖（LPS）的影响。在一系列越来越严格的提取缓冲液中处理肝脏切片，以通过溶解度分离蛋白质。使用液相色谱/串联质谱法（LC-MS/MS）鉴定提取的蛋白质。乙醇和LPS均显著增加基质体蛋白的数量~ 25%。乙醇预暴露增强LPS诱导的肝损伤与独特的蛋白质变化有关。对富集肝细胞外基质的提取方法进行了表征。结果表明，肝基质体动态响应急性（LPS）和慢性（乙醇）的压力，更戏剧性的肝纤维化的变化发生之前很久。肥大体的变化可能有助于，至少部分地，对这些压力的病理反应。同样有趣的是，几种ECM蛋白对两种应力的反应相似，表明两种模型中存在共同的机制。然而，对于单独和组合暴露，存在独特的反应。
The extracellular matrix (ECM) consists of diverse components that work bidirectionally with surrounding cells to create a responsive microenvironment. In some contexts (e.g., hepatic fibrosis), changes to the ECM are well recognized and understood. However, it is becoming increasingly accepted that the hepatic ECM proteome (i.e., matrisome) responds dynamically to stress well before fibrosis. The term “transitional tissue remodeling” describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these changes in ECM may contribute to early disease initiation and/or progression. The nature and magnitude of these changes to the ECM in liver injury are poorly understood. The goals of this work were to validate analysis of the ECM proteome and compare the impact of 6 weeks of ethanol diet and/or acute lipopolysaccharide (LPS). Liver sections were processed in a series of increasingly rigorous extraction buffers to separate proteins by solubility. Extracted proteins were identified using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Both ethanol and LPS dramatically increased the number of matrisome proteins ~25%. The enhancement of LPS-induced liver damage by ethanol preexposure was associated with unique protein changes. An extraction method to enrich the hepatic ECM was characterized. The results demonstrate that the hepatic matrisome responds dynamically to both acute (LPS) and chronic (ethanol) stresses, long before more-dramatic fibrotic changes to the liver occur. The changes to the mastrisome may contribute, at least in part, to the pathological responses to these stresses. It is also interesting that several ECM proteins responded similarly to both stresses, suggesting a common mechanism in both models. Nevertheless, there were responses that were unique to the individual and combined exposures.