title: Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.
abstract: 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.
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baiocchini
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Montaldo
authors.affiliation: Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome and Istituto Pasteur - Fondazione Cenci Bolognetti, Via Regina Elena 324, 00161 Rome, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Conigliaro
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Grimaldi
authors.affiliation: Dipartimento di Scienze Biochimiche, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Correani
authors.affiliation: Dipartimento di Chimica, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mura
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ciccosanti
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Nicolina
authors.initials: N
authors.lastname: Rotiroti
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Brenna
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Montalbano
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Via Divisi 83-90133, Palermo, Italy.|Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council of Italy, Palermo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.|Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.affiliation: Dipartimento di Scienze Biochimiche, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.affiliation: Dipartimento di Scienze Biochimiche, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Maras
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Del Nonno
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.|Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome and Istituto Pasteur - Fondazione Cenci Bolognetti, Via Regina Elena 324, 00161 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, via Portuense 292, 00149 Rome, Italy.|Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome and Istituto Pasteur - Fondazione Cenci Bolognetti, Via Regina Elena 324, 00161 Rome, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Mancone
mesh_terms: D000818:Animals; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism*; D016174:Hepacivirus / Q000502:physiology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051379:Mice; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D020543:Proteome