Abstract
Hepatic stellate cells (HSCs) serve as the main body storage compartment for vitamin A through retinyl ester (RE)-filled lipid droplets (LDs). Upon liver injury, HSCs adopt a myofibroblastic phenotype characterized by an elevated expression of extracellular matrix proteins and a concomitant loss of LDs. On the one hand, LD breakdown has been suggested to provide the energy required for HSC activation into myofibroblast-like cells. On the other hand, this process could mitigate HSC activation following the transformation of released REs into retinoic acids (RAs), ligands for nuclear receptors exerting antifibrotic transcriptional regulatory activities in HSCs. Importantly, RAs may also constitute a means for HSCs to orchestrate the liver response to injury by triggering transcriptional effects in multiple additional surrounding liver cell populations. We envision that new approaches, such as single-cell technologies, will allow to better define how RAs are issued from LD loss in HSCs exert a multicellular control of the liver (patho)physiology.
Highlights
While the liver is composed mainly of hepatocytes, additional less abundant cell-types contribute significantly to hepatic physiology
Hepatic stellate cells (HSCs), which are localized within the space of Disse between endothelial cells and hepatocytes, are mesenchymal-like cells making up about 10% of the total liver cell population [1]
We propose that retinoic acids (RAs) may exert protective effects upon liver injuries through activities in non-parenchymal cells
Summary
While the liver is composed mainly of hepatocytes, additional less abundant cell-types contribute significantly to hepatic (patho) physiology. Hepatic stellate cells (HSCs), which are localized within the space of Disse between endothelial cells and hepatocytes, are mesenchymal-like cells making up about 10% of the total liver cell population [1]. Process, described as a “transdifferentiation” towards a myofibroblast-like phenotype accompanied by a loss of the lipid droplets (LDs) characterizing their quiescent state [2]. Activated HSCs synthesize large amounts of ECM proteins, such as type I and type III collagen, and are key players in the resolution of liver injury. Uncontrolled HSC activation is a major contributor to liver fibrosis, which has put a spotlight on this cell type within the last decades [3]
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