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Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks.

Carpino G, Renzi A, Onori P, Gaudio E - Int J Mol Sci (2013)

Bottom Line: HPC activation determines the appearance of a ductular reaction.In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs.Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome 00161, Italy. guido.carpino@uniroma1.it.

ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs) activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis.

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Related in: MedlinePlus

Cartoon indicating possible molecular cross-talks involving hepatic stellate cells (HSCs), hepatic progenitor cells (HPCs) and liver macrophages. In NAFLD, HPCs highly proliferate determining the appearance of ductular reaction (DR). HPC proliferation is determined by the up-regulation of both Wnt and Notch pathways. DR can produce several fibrogenetic factors such as TGF-β and PDGF which, in turn, activate portal myofibroblasts and HSCs to produce type 1 collagen. In parallel, the HPCs could differentiate towards hepatocytes; this process is characterized by a down-regulation of Notch signal and could be driven by macrophage Wnt3a secretion. PV = portal vein; BD = bile duct.
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f3-ijms-14-20112: Cartoon indicating possible molecular cross-talks involving hepatic stellate cells (HSCs), hepatic progenitor cells (HPCs) and liver macrophages. In NAFLD, HPCs highly proliferate determining the appearance of ductular reaction (DR). HPC proliferation is determined by the up-regulation of both Wnt and Notch pathways. DR can produce several fibrogenetic factors such as TGF-β and PDGF which, in turn, activate portal myofibroblasts and HSCs to produce type 1 collagen. In parallel, the HPCs could differentiate towards hepatocytes; this process is characterized by a down-regulation of Notch signal and could be driven by macrophage Wnt3a secretion. PV = portal vein; BD = bile duct.

Mentions: The local cellular microenvironment has a key role in achieving a defined progenitor specification and driving the acquirement of divergent cell fates in response to diverse diseases [49]. The study of well-described stem cell niches in other organs (intestinal, hair-follicle and the haematopoietic stem cell compartment) has indicated that Wnt and Notch signalling pathways are key regulators of stem cell proliferation and fate choice (Figure 3) [57].


Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks.

Carpino G, Renzi A, Onori P, Gaudio E - Int J Mol Sci (2013)

Cartoon indicating possible molecular cross-talks involving hepatic stellate cells (HSCs), hepatic progenitor cells (HPCs) and liver macrophages. In NAFLD, HPCs highly proliferate determining the appearance of ductular reaction (DR). HPC proliferation is determined by the up-regulation of both Wnt and Notch pathways. DR can produce several fibrogenetic factors such as TGF-β and PDGF which, in turn, activate portal myofibroblasts and HSCs to produce type 1 collagen. In parallel, the HPCs could differentiate towards hepatocytes; this process is characterized by a down-regulation of Notch signal and could be driven by macrophage Wnt3a secretion. PV = portal vein; BD = bile duct.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3821605&req=5

f3-ijms-14-20112: Cartoon indicating possible molecular cross-talks involving hepatic stellate cells (HSCs), hepatic progenitor cells (HPCs) and liver macrophages. In NAFLD, HPCs highly proliferate determining the appearance of ductular reaction (DR). HPC proliferation is determined by the up-regulation of both Wnt and Notch pathways. DR can produce several fibrogenetic factors such as TGF-β and PDGF which, in turn, activate portal myofibroblasts and HSCs to produce type 1 collagen. In parallel, the HPCs could differentiate towards hepatocytes; this process is characterized by a down-regulation of Notch signal and could be driven by macrophage Wnt3a secretion. PV = portal vein; BD = bile duct.
Mentions: The local cellular microenvironment has a key role in achieving a defined progenitor specification and driving the acquirement of divergent cell fates in response to diverse diseases [49]. The study of well-described stem cell niches in other organs (intestinal, hair-follicle and the haematopoietic stem cell compartment) has indicated that Wnt and Notch signalling pathways are key regulators of stem cell proliferation and fate choice (Figure 3) [57].

Bottom Line: HPC activation determines the appearance of a ductular reaction.In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs.Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome 00161, Italy. guido.carpino@uniroma1.it.

ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs) activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis.

Show MeSH
Related in: MedlinePlus