Zhang Wen, Zhang Ning, Wu Wenyue, Li Hong, You Hong, Chen Wei
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Front Pharmacol. 2024 Sep 2;15:1435359. doi: 10.3389/fphar.2024.1435359. eCollection 2024.
The excessive deposition and cross-linking of core matrisome components typically result in abnormal remodeling of the extracellular matrix (ECM), leading to increased liver stiffness and worsening liver fibrosis. Exploring the biochemical properties of the ECM scaffold can deepen our understanding of the pathological mechanisms driving liver fibrosis and potentially facilitate the identification of therapeutic targets. While traditional sodium dodecyl sulfate (SDS)-based liver decellularization followed by proteomics can uncover the matrisome components within the ECM scaffold, it lacks the ability to reveal physicochemical characteristics like solubility. In our present study, using adult mouse liver as an example, we introduced a novel two-step workflow that combines our previously enhanced SDS (ESDS) decellularization with the conventional SDS method, enabling the identification of matrisome members with mild and/or high solubilities. Through this approach, we visualized the atlas of the mildly and highly insoluble matrisome contents in the adult mouse liver, as well as the regulatory network of highly insoluble matrisome that largely governs liver stiffness. Given the strong correlation between increased matrisome insolubility and heightened ECM stiffness, we believe that this methodology holds promise for future research focused on liver stiffness.
核心基质组分组分的过度沉积和交联通常会导致细胞外基质（ECM）异常重塑，进而导致肝脏硬度增加和肝纤维化加重。探索ECM支架的生化特性可以加深我们对驱动肝纤维化的病理机制的理解，并可能有助于确定治疗靶点。虽然传统的基于十二烷基硫酸钠（SDS）的肝脏去细胞化处理后进行蛋白质组学分析可以揭示ECM支架内的基质组成分，但它缺乏揭示诸如溶解度等物理化学特性的能力。在我们目前的研究中，以成年小鼠肝脏为例我们引入了一种新颖的两步工作流程，该流程将我们之前改进的SDS（ESDS）去细胞化方法与传统的SDS方法相结合，能够鉴定出具有轻度和/或高溶解度的基质组成员。通过这种方法，我们可视化了成年小鼠肝脏中轻度和高度不溶性基质组成分的图谱，以及在很大程度上控制肝脏硬度的高度不溶性基质组的调控网络。鉴于基质组不溶性增加与ECM硬度升高之间存在很强的相关性，我们相信这种方法对未来聚焦于肝脏硬度的研究具有前景。
