Panebianco, C;
Oben, JA;
Vinciguerra, M;
Pazienza, V;
(2016)
Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings.
Clinical and Experimental Medicine
, 17
(3)
pp. 269-280.
10.1007/s10238-016-0438-x.
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Abstract
Hepatic stellate cells (HSCs), also known as perisinusoidal cells, are pericytes found in the perisinusoidal space of the liver. HSCs are the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage. When the liver is damaged, stellate cells can shift into an activated state, characterized by proliferation, contractility and chemotaxis. The activated HSCs secrete collagen scar tissue, which can lead to cirrhosis. Recent studies have shown that in vivo activation of HSCs by fibrogenic agents can eventually lead to senescence of these cells, which would contribute to reversal of fibrosis although it may also favor the insurgence of liver cancer. HSCs in their non-active form store huge amounts of retinoic acid derivatives in lipid droplets, which are progressively depleted upon cell activation in injured liver. Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A, generally required for growth and development. The precise function of retinoic acid and its alterations in HSCs has yet to be elucidated, and nonetheless in various cell types retinoic acid and its receptors (RAR and RXR) are known to act synergistically with peroxisome proliferator-activated receptor gamma (PPAR-gamma) signaling through the activity of transcriptional heterodimers. Here, we review the recent advancements in the understanding of how retinoic acid signaling modulates the fibrogenic potential of HSCs and proposes a synergistic combined action with PPAR-gamma in the reversal of liver fibrosis.
| Type: | Article |
|---|---|
| Title: | Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s10238-016-0438-x |
| Publisher version: | https://doi.org/10.1007/s10238-016-0438-x |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Medicine, Research & Experimental, Research & Experimental Medicine, Hepatic stellate cells, Retinoic acid, Fibrogenesis, PROLIFERATOR-ACTIVATED-RECEPTOR, HISTONE DEACETYLASE INHIBITORS, ANTIGEN-PRESENTING CELLS, FAT-STORING CELLS, VITAMIN-A, CELLULAR SENESCENCE, HUMAN FIBROBLASTS, GENE-EXPRESSION, UP-REGULATION, ITO-CELLS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10045467 |
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