2019
DOI: 10.3390/ijms20102507
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Epigenetic Mechanisms in Hepatic Stellate Cell Activation During Liver Fibrosis and Carcinogenesis

Abstract: Liver fibrosis is an essential component of chronic liver disease (CLD) and hepatocarcinogenesis. The fibrotic stroma is a consequence of sustained liver damage combined with exacerbated extracellular matrix (ECM) accumulation. In this context, activation of hepatic stellate cells (HSCs) plays a key role in both initiation and perpetuation of fibrogenesis. These cells suffer profound remodeling of gene expression in this process. This review is focused on the epigenetic alterations participating in the transdi… Show more

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Cited by 54 publications
(48 citation statements)
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“…Fibrogenesis is normally a wound healing response to an acute or transient injury to an organ, which architecture is restored afterwards. However, when the injury is perpetuated as in CLD, this wound healing response is sustained and leads to the accumulation of extracellular matrix (ECM), an event known as hepatic fibrogenesis [ 3 , 4 , 5 ]. The fibrosis end-phase is known as cirrhosis, which involves the substitution of liver parenchyma for scar tissue, the alteration of the organ’s architecture and the impairment of liver function due in part to the dedifferentiation of hepatocytes [ 6 , 7 ].…”
Section: Introductionmentioning
confidence: 99%
See 2 more Smart Citations
“…Fibrogenesis is normally a wound healing response to an acute or transient injury to an organ, which architecture is restored afterwards. However, when the injury is perpetuated as in CLD, this wound healing response is sustained and leads to the accumulation of extracellular matrix (ECM), an event known as hepatic fibrogenesis [ 3 , 4 , 5 ]. The fibrosis end-phase is known as cirrhosis, which involves the substitution of liver parenchyma for scar tissue, the alteration of the organ’s architecture and the impairment of liver function due in part to the dedifferentiation of hepatocytes [ 6 , 7 ].…”
Section: Introductionmentioning
confidence: 99%
“…The fibrosis end-phase is known as cirrhosis, which involves the substitution of liver parenchyma for scar tissue, the alteration of the organ’s architecture and the impairment of liver function due in part to the dedifferentiation of hepatocytes [ 6 , 7 ]. Cirrhosis markedly increases the chances of developing hepatocellular carcinoma (HCC), the most frequent type of liver cancer [ 3 , 5 , 8 ]. From 1990 to 2017 cirrhosis-caused deaths increased from less than 900,000 to more than 1.32 million per year globally.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…If the injury persists, liver fibrosis can progress to cirrhosis and ultimately result in the development of liver cancer (Affo et al, 2017). Hepatic stellate cells (HSCs) are the major cell type responsible for liver fibrogenesis (Barcena-Varela et al, 2019). Upon liver injury, HSCs become activated and transdifferentiate into myofibroblast-like cells that proliferate and migrate to regions of hepatocyte injury and produce collagen and a-smooth muscle actin (a-SMA) (Barcena-Varela et al, 2019).…”
Section: Introductionmentioning
confidence: 99%
“…Hepatic stellate cells (HSCs) are the major cell type responsible for liver fibrogenesis (Barcena-Varela et al, 2019). Upon liver injury, HSCs become activated and transdifferentiate into myofibroblast-like cells that proliferate and migrate to regions of hepatocyte injury and produce collagen and a-smooth muscle actin (a-SMA) (Barcena-Varela et al, 2019). HSC activation is driven by multiple mediators, such as transforming growth factor-b1 (TGF-b1), platelet-derived growth factor, and tumor necrosis factor-a (Dewidar et al, 2019).…”
Section: Introductionmentioning
confidence: 99%