title: Cellular and molecular mechanisms in liver fibrogenesis.
abstract: Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process, potentially reversible, that drives the progression of chronic liver diseases (CLD) towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), the pro-fibrogenic effector cells, originate mainly from activation of hepatic stellate cells and portal fibroblasts being characterized by a proliferative and survival attitude. MFs also contract in response to vasoactive agents, sustain angiogenesis and recruit and modulate activity of cells of innate or adaptive immunity. Chronic activation of wound healing and oxidative stress as well as derangement of epithelial-mesenchymal interactions are "major" pro-fibrogenic mechanisms, whatever the etiology. However, literature has outlined a complex network of pro-fibrogenic factors and mediators proposed to modulate CLD progression, with some of them being at present highly debated in the field, including the role of epithelial to mesenchymal transition and Hedgehog signaling pathways. Hypoxia and angiogenesis as well as inflammasomes are recently emerged as ubiquitous pro-inflammatory and pro-fibrogenic determinants whereas adipokines are mostly involved in CLD related to metabolic disturbances (metabolic syndrome and/or obesity and type 2 diabetes). Finally, autophagy as well as natural killer and natural killer-T cells have been recently proposed to significantly affect fibrogenic CLD progression.
authors.affiliation: University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Novo
authors.affiliation: University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cannito
authors.affiliation: University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Paternostro
authors.affiliation: University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bocca
authors.affiliation: University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Miglietta
authors.affiliation: University of Torino, Dept. Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, Corso Raffaello 30, 10125 Torino, Italy. Electronic address: maurizio.parola@unito.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D058628:Myofibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress
keywords: Chronic inflammation; Chronic liver injury; Extracellular matrix; Fibrogenic mechanisms; Hepatic myofibroblasts; Liver fibrogenesis