Hepatic stellate cell (vitamin A‐storing cell) and its relative – past, present and future

Abstract

HSCs (hepatic stellate cells) (also called vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells or Ito cells) exist in the space between parenchymal cells and liver sinusoidal endothelial cells of the hepatic lobule and store 50-80% of vitamin A in the whole body as retinyl palmitate in lipid droplets in the cytoplasm. In physiological conditions, these cells play pivotal roles in the regulation of vitamin A homoeostasis. In pathological conditions, such as hepatic fibrosis or liver cirrhosis, HSCs lose vitamin A and synthesize a large amount of extracellular matrix components including collagen, proteoglycan, glycosaminoglycan and adhesive glycoproteins. Morphology of these cells also changes from the star-shaped SCs (stellate cells) to that of fibroblasts or myofibroblasts. The hepatic SCs are now considered to be targets of therapy of hepatic fibrosis or liver cirrhosis. HSCs are activated by adhering to the parenchymal cells and lose stored vitamin A during hepatic regeneration. Vitamin A-storing cells exist in extrahepatic organs such as the pancreas, lungs, kidneys and intestines. Vitamin A-storing cells in the liver and extrahepatic organs form a cellular system. The research of the vitamin A-storing cells has developed and expanded vigorously. The past, present and future of the research of the vitamin A-storing cells (SCs) will be summarized and discussed in this review.

Vitamin A Supplementation Transiently Increases Retinol Concentrations in Extrahepatic Organs of Neonatal Rats Raised under Vitamin A–Marginal Conditions

“…This observation was similar to findings in neonatal piglets, in which the liver ranked as the highest in terms of retinol concentration, followed by the kidneys and lungs, irrespective of VA treatment (23). However, kinetic studies in rats supplemented with VARA have shown a dramatic stimulatory effect of supplementation on the uptake and retention of retinyl esters by the lungs and intestine (14,36), consistent with the previously demonstrated role of retinoic acid in upregulating genes responsible for VA storage (37)(38)(39). Based on these results, we speculate that VA alone may not be as effective as VARA in promoting extrahepatic retinol deposition, although future kinetic analyses of our data are needed to confirm this hypothesis.…”

Retinol Binding Protein-Albumin Domain III Fusion Protein Deactivates Hepatic Stellate Cells

“…Vitamin A (retinol), acquired from the diet, circulates bound to retinol binding protein (RBP) in the bloodstream, and it is taken up initially by liver cells and transferred to HSCs via the RBP receptor (Kawaguchi et al, 2007;Senoo et al, 2010). HSCs store approximately 80% of vitamin A in the whole body as retinyl esters in cytoplasmic lipid droplets.…”

Bone morphogenetic protein 7 suppresses the progression of hepatic fibrosis and regulates the expression of gremlin and transforming growth factor β1

“…In this well-regulated process, vitamin A-storing HSCs are converted into contractile myofibroblasts (activated HSCs), characterized by an increased expression of α-SMA, collagen and the production of various fibrosis-related cytokines, such as transforming growth factor (TGF)-β, constructive tissue growth factor (CTGF), tissue inhibitors of matrix metalloproteinases (TIMPs), orchestrating the complex molecular regulatory system underlying fibrogenesis (7,8). Among the large number of cytokines and growth factors in the progression of hepatic fibrosis, TGF-β signaling is considered a key determinant, owing to emerging evidence indicating that TGF-β is a critical fibrinogenic and proliferative stimulus to HSCs during fibrogenesis (9,10).…”