Hepatic myofibroblasts and fibrogenic progression of chronic liver diseases
Erica Novo1,2, Stefania Cannito1,2, Elisabetta Morello1,2, Claudia Paternostro1,2, Claudia Bocca1,2, Antonella Miglietta1,2 and Maurizio Parola1,2
1Department of Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical
Pathology and 2Interuniversity Centre of Hepatic Pathophysiology, University of Torino, Italy
Offprint requests to: Prof. Maurizio Parola, Deptartment of Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, School of Medicine - University of Torino, C.so Raffaello 30, 10125 Torino, Italy. e-mail: maurizio.parola@unito.it
Summary. Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process that during the course of a chronic liver disease (CLD) leads progressively to an excess deposition of extracellular matrix (ECM) components in an attempt to limit the consequences of chronic parenchymal injury. Irrespective of etiology, liver fibrogenesis is sustained and modulated by an intense cross talk occurring between different hepatic cell populations that involves the synthesis and release of several mediators, including growth factors, cytokines, chemokines, reactive oxygen species, adipokines, vasoactive agents and plasma proteins. In this scenario a major pro-fibrogenic role is played by a heterogeneous population of α-smooth muscle actin (α-SMA) positive cells defined as hepatic myofibroblasts (MFs). Hepatic MFs are highly proliferative and contractile cells, primarily responsible for excess deposition of ECM components and involved in ECM altered remodeling observed in CLDs. MFs also represent a unique and critical cellular crossroad able to integrate incoming paracrine or autocrine signals, released from all hepatic cell populations involved or available in the microenvironment, as well as to synthetize and release mediators which sustain and perpetuate fibrogenesis, chronic inflammatory response and neo-angiogenesis. This review has been designed to offer critical knowledge on hepatic MFs, including terminology, essential definitions and characterization of MFs, with a focus on the origin of these cells (mainly from hepatic stellate cells and portal fibroblasts or, to a lesser extent, bone marrow-derived cells), the process of activation and the functional responses that these cells can operate in the fibrogenic progression of CLDs. Histol Histopathol 30, 1011-1032 (2015)
Key words: Hepatic myofibroblasts, Hepatic stellate cells, Portal myofibroblasts, Liver fibrogenesis, Chronic liver diseases, Liver angiogenesis
DOI: 10.14670/HH-11-623