Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution

被引：176

作者：

Baiocchini, Andrea ^{[1
]}

Montaldo, Claudia ^{[1
]}

Conigliaro, Alice ^{[2
,3
]}

Grimaldi, Alessio ^{[1
]}

Correani, Virginia ^{[4
]}

Mura, Francesco ^{[5
]}

Ciccosanti, Fabiola ^{[1
]}

Rotiroti, Nicolina ^{[1
]}

Brenna, Alessia ^{[1
]}

Montalbano, Marzia ^{[1
]}

D'Offizi, Gianpiero ^{[1
]}

Capobianchi, Maria Rosaria ^{[1
]}

Alessandro, Riccardo ^{[6
,7
]}

Piacentini, Mauro ^{[1
,8
]}

Schinina, Maria Eugenia ^{[4
]}

Maras, Bruno ^{[4
]}

Del Nonno, Franca ^{[1
]}

Tripodi, Marco ^{[1
,2
,3
]}

Mancone, Carmine ^{[1
,2
,3
]}

机构：

[1] IRCCS, Natl Inst Infect Dis L Spallanzani, Via Portuense 292, I-00149 Rome, Italy

[2] Univ Roma La Sapienza, Dept Cellular Biotechnol & Haematol, Via Regina Elena 324, I-00161 Rome, Italy

[3] Fdn Cenci Bolognetti, Ist Pasteur, Via Regina Elena 324, I-00161 Rome, Italy

[4] Univ Roma La Sapienza, Dipartimento Sci Biochim, Ple Aldo Moro 5, I-00185 Rome, Italy

[5] Univ Roma La Sapienza, Dipartimento Chim, Ple Aldo Moro 5, I-00185 Rome, Italy

[6] Univ Palermo, Dipartimento Biopatol & Biotecnol Med, Via Divisi 83, I-90133 Palermo, Italy

[7] Natl Res Council Italy, IBIM, Palermo, Italy

[8] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy

来源：

PLOS ONE | 2016年 / 11卷 / 03期

关键词：

VI COLLAGEN; EXPRESSION; TISSUE; PROTEIN; MICE;

D O I：

10.1371/journal.pone.0151736

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis). Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

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