Extracellular matrix molecular remodeling in human liver fibrosis evolution

Andrea Baiocchini, Claudia Montaldo, Alice Conigliaro, Alessio Grimaldi, Virginia Correani, Francesco Mura, Fabiola Ciccosanti, Nicolina Rotiroti, Alessia Brenna, Marzia Montalbano, Gianpiero D'Offizi, Maria Rosaria Capobianchi, Riccardo Alessandro, Mauro Piacentini, Maria Eugenia Schininà, Bruno Maras, Franca Del Nonno, Marco Tripodi, Carmine Mancone

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere0151736
JournalPLoS One
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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