The alterations in the extracellular matrix composition guide the repair of damaged liver tissue.
The alterations in the extracellular matrix composition guide the repair of damaged liver tissue.
复制标题
细胞外基质组合物的改变指导受损的肝组织的修复。
DOI：
10.1038/srep27398
复制
发表时间：
2016-06-06
影响因子：
4.6
通讯作者：
Jaks V
中科院分区：
文献类型：
--
作者：
Klaas M;Kangur T;Viil J;Mäemets-Allas K;Minajeva A;Vadi K;Antsov M;Lapidus N;Järvekülg M;Jaks V
虽然肝再生的细胞机制已被彻底研究，细胞外基质（ECM）在肝再生中的作用仍然知之甚少。我们利用蛋白质组学为基础的方法，以确定CCl 4或DDC治疗后的ECM组成的变化，并结合生物物理和细胞培养方法研究其对肝细胞增殖的影响。我们确定了ECM结构组分（如胶原蛋白I、IV、V、纤连蛋白、弹性蛋白）以及非结构蛋白（如嗅介蛋白-4、血小板反应蛋白-4、含有犰狳重复序列的X-连接蛋白2（Armcx 2））的显著变化。在受损的人类肝脏中观察到ECM组成的类似变化。胶原含量的增加和弹性纤维的减少导致受损肝脏ECM的重排和刚度增加。有趣的是，ECM成分的改变是不均匀的，门静脉周围和中央周围区域之间存在差异，因此我们的实验证明了所选ECM成分调节肝细胞和胆管细胞增殖的差异能力。我们首次定义了从损伤中恢复的肝脏ECM组成的改变，并提出了协调ECM重塑的功能证据，以确保有效恢复肝脏组织。
While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue.