Hepatic stellate cells retain retinoid-laden lipid droplets after cellular transdifferentiation into activated myofibroblasts.

American Journal of Physiology. Gastrointestinal and Liver Physiology
Loretta L JophlinDon C Rockey

Abstract

Loss of retinyl ester (RE)-rich lipid droplets (LDs) from hepatic stellate cells (HSCs) is cited as a key event in their cellular transdifferentiation to activated, pro-fibrotic myofibroblasts; however, it remains unclear if changes in LD morphology or RE content are causal for transdifferentiation. To better understand LD dynamics in vitro within a common model of HSC activation, we used novel approaches preserving LD morphology and allowing for quantitation of RE. The size and quantity of LDs within in vitro and in vivo bile duct ligation (BDL)-activated HSCs were quantitated using adipocyte differentiation-related protein (ADRP) labeling and oil red o (ORO) staining (gold standard), and RE content was determined using fluorescence microscopy. We found during HSC activation in vitro that LD number differed significantly when measured by ADRP and ORO, respectively ( day 1: 56 vs. 5, P = 0.03; day 4: 101 vs. 39, P = 0.03; day 14: 241 vs. 12, P = 0.02). Ex vivo HSCs activated in vivo contained the same number of LDs as day 4 in vitro activated HSCs (118 vs. 101, P = 0.54). Decline in LD RE occurred beyond day 4 in vitro and day 1 ex vivo , after HSC transdifferentiation was underway. Lastly, in situ HSCs examined using electron ...Continue Reading

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Citations

Mar 14, 2019·Current Opinion in Gastroenterology·Don C Rockey
Mar 4, 2020·Scientific Reports·Céline HoffmannVirginie Escriou
Oct 20, 2019·Pharmacology & Therapeutics·Suya WangAlexander R Moise
Feb 3, 2021·Gastroenterology·Don C Rockey, Scott L Friedman
Feb 8, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sara Brin RosenthalDavid A Brenner

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Methods Mentioned

BETA
electron microscopy
fluorescence microscopy
light microscopy
fluorescence photomicroscopy
transmission electron microscopy

Software Mentioned

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