A novel role for hepatic stellate cells in pathogenesis of visceral leishmaniasis

Shoukry, Naglaa H.; Fabre, Thomas; Gandhi, Chandrashekhar R.

doi:10.1002/hep.28247

Cited by 7 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). Importantly, it is well known that LDs of HSCs mainly contain retinol, triglycerides and cholesterol [5], [6], [7], [8], [9], [10]. Therefore, we detected the level of retinol, triglycerides and cholesterol from quiescent HSCs to activated HSCs, respectively.…”

Section: Resultsmentioning

confidence: 94%

“…Generally, it is agreed that retinol and triglyceride are present at similar concentrations in LDs obtained from primary rat HSCs isolated from well-nourished rats [5], [6], [7], [8]. Besides, cholesterol, cholesteryl ester, phospholipids and free fatty acids are also reported to be present in rat HSC LDs [5], [6], [7], [8].…”

Section: Discussionmentioning

confidence: 94%

“…3F). Furthermore, main components of LDs, retinol, triglyceride and cholesterol [5], [6], [7], [8], [9], [10], were determined to reveal changes of LD content in activated HSCs. A nearly 1.5-fold increase in retinol, triglyceride and cholesterol content could be evidenced (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…HSCs were initially termed “fat-storing cells”, which derives from the large amount of neutral lipids that are stored in numerous LDs in the cytosol [5], [6], [7], [8]. Generally, it is agreed that retinol and triglyceride are present at similar concentrations in LDs obtained from primary rat HSCs isolated from well-nourished rats [5], [6], [7], [8].…”

Section: Discussionmentioning

confidence: 99%

“…Liver fibrosis and early cirrhosis are dynamic and reversible, thus efforts to modulate the fibrogenesis process are important for preventive treatment of cirrhosis and hepatic failure [4]. The transdifferentiation of hepatic stellate cells (HSCs) into contractile, matrix-producing myofibroblasts (MFBs) is a central event in hepatic fibrogenesis [5], [6], [7]. In healthy liver, quiescent HSCs store 80% of total liver retinols and normally maintain lipocyte phenotype characterized by storage of lipid droplets (LDs) in the cytoplasm [8].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Autophagy regulates turnover of lipid droplets via ROS-dependent Rab25 activation in hepatic stellate cell

et al. 2017

View full text Add to dashboard Cite

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by dramatic disappearance of lipid droplets (LDs). Although LD disappearance has long been considered one of the hallmarks of HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of autophagy in the process of LD disappearance, and to further examine the underlying mechanisms in this molecular context. We found that LD disappearance during HSC activation was associated with a coordinate increase in autophagy. Inhibition or depletion of autophagy by Atg5 siRNA impaired LD disappearance of quiescent HSCs, and also restored lipocyte phenotype of activated HSCs. In contrast, induction of autophagy by Atg5 plasmid accelerated LD loss of quiescent HSCs. Importantly, our study also identified a crucial role for reactive oxygen species (ROS) in the facilitation of autophagy activation. Antioxidants, such as glutathione and N-acetyl cysteine, significantly abrogated ROS production, and in turn, prevented autophagosome generation and autophagic flux during HSC activation. Besides, we found that HSC activation triggered Rab25 overexpression, and promoted the combination of Rab25 and PI3KCIII, which direct autophagy to recognize, wrap and degrade LDs. Down-regulation of Rab25 activity, using Rab25 siRNA, blocked the target recognition of autophagy on LDs, and inhibited LD disappearance of quiescent HSCs. Moreover, the scavenging of excessive ROS could disrupt the interaction between autophagy and Rab25, and increase intracellular lipid content. Overall, these results provide novel implications to reveal the molecular mechanism of LD disappearance during HSC activation, and also identify ROS-Rab25-dependent autophagy as a potential target for the treatment of liver fibrosis.

show abstract