The role and fate of vitamin A storage in lipid droplets during activation and reversion of the hepatic stellate cells

Evering, Hester (2019) The role and fate of vitamin A storage in lipid droplets during activation and reversion of the hepatic stellate cells. Bachelor's Thesis, Pharmacy.

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Abstract

Hepatic stellate cells are cells in the liver that have characteristic lipid droplets, in which they store retinoids. In a healthy situation, these cells are present in a quiescent state. During chronic liver injury, the hepatic stellate cell becomes activated and changes into a myofibroblast. This activated hepatic stellate cell starts producing extracellular matrix (ECM) proteins and the activation is accompanied by a loss of these lipid droplets. In case of regression of the chronic liver injury, either spontaneous or drug-induced, this activated hepatic stellate cell could return to a quiescent-like state, that is different from the quiescent hepatic stellate cell. In this reverted cell, the fibrogenic genes are downregulated and the lipid droplets are restored. In this review the role and the fate of the retinoid storage in the lipid droplets and related proteins are discussed during activation and regression. In the quiescent hepatic stellate cell cytoplasmic retinoid-lipid droplets are present containing proteins as well, that are necessary for lipid and retinoid metabolism. During activation, the lipid droplets in the hepatic stellate cell become smaller and some of them get lost by various mechanisms, resulting in the release of the content. The expression of some proteins, that are present in the lipid droplets or hepatic stellate cell, like Rab18 and retinoid receptors, changes as well during activation and this change could be important, because it could regulate the loss of lipid droplets in the hepatic stellate cell. The release of retinoids could have antifibrotic effects, as well as an effect on the expression of lipid droplet-associated proteins, like perilipins or Rab18. During reversion, there is a recovery of the lipid droplets and the retinoid metabolism and storage. Also, some proteins, like ATG2A, perilipins or ADRP, are important in the reverted hepatic stellate cell, with regard to regulation of the reversion. The differences between the expression of some related genes, like PPARγ, are relevant as well and their role is discussed in this review. Finally, retinoids have protective effects on other cells of the liver. With the provided knowledge, the transformation of hepatic stellate cells and resolution of fibrosis could be assessed.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Beljaars, E.
Degree programme:	Pharmacy
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	28 May 2019
Last Modified:	04 Jun 2019 10:35
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/19544

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