Browsing by Subject "Hepatic myofibroblasts"

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    Hepatic myofibroblasts and fibrogenic progression of chronic liver diseases
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Novo, Erica; Cannito, Stefania; Morello, Elisabetta; Paternostro, Claudia; Bocca, Claudia; Miglietta, Antonella; Parola, Maurizio
    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.
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    Liver fibrosis: a dynamic and potentially reversible process
    (Murcia : F. Hernández, 2010) Povero, Davide; Busletta, Chiara; Novo, Erica; Valfrè di Bonzo, Lorenzo; Cannito, Stefania; Paternostro, Claudia; Parola, Maurizio
    In any chronic liver disease (CLDs), whatever the aetiology, reiteration of liver injury results in persisting inflammation and progressive fibrogenesis, with chronic activation of the wound healing response in CLDs, representing a major driving force for progressive accumulation of ECM components, eventually leading to liver cirrhosis. Cirrhosis is characterized by fibrous septa dividing the hepatic parenchyma into regenerative pseudo-lobules, as well as by extensive changes in vascular architecture, the development of portal hypertension and related complications. Liver fibrogenesis (i.e., the dynamic process leading to increased deposition of ECM and much more) can lead to different patterns of fibrosis and is sustained by myofibroblast-like cells (MFs) of different origin, with activated hepatic stellate cells (HSC/MFs) being the major cell type involved. Major pro-fibrogenic mechanisms also include oxidative stress, as well as derangement of epithelial-mesenchymal interactions and, as recently suggested, the process of epithelial to mesenchymal transition (EMT). Liver fibrosis has been considered traditionally as an irreversible process but experimental and clinical literature data published in the last decade have suggested that both the removal of the aetiological agent or condition, as well as an effective therapy, can result in significant regression of liver fibrosis. This is usually associated, particularly in animal models, with induction of apoptosis in MFs but, unfortunately, human HSC/MFs are much more resistant to apoptosis than murine MFs. However, clinical studies provided no unequivocal evidence for a complete reversal of cirrhosis or a significant reversal of vascular changes in conditions of established cirrhosis.