Abstract
Comprehending the molecular mechanisms underlying hepatic fibrogenesis is essential to the development of treatment. The hallmark of hepatic fibrosis is the development and deposition of excess fibrous connective tissue forcing tissue remodeling. Hepatic stellate cells (HSC) play a major role in the pathogenesis of liver fibrosis. Their activation via the transforming growth factor-β1 (TGF-β1) as a key mediator is considered the crucial event in the pathophysiology of hepatic fibrogenesis. It has been shown that Perilipin 5 (PLIN5), known as a lipid droplet structural protein that is highly expressed in oxidative tissue, can inhibit such activation through various mechanisms associated with lipid metabolism. This study aimed to investigate the possible influence of PLIN5 on TGF-β1 signaling. Our findings confirm the importance of PLIN5 in maintaining HSC quiescence in vivo and in vitro. PLIN5 overexpression suppresses the TGF-β1-SMAD2/3 and SNAIL signaling pathways as well as the activation of the signal transducers and activators of transcription 3 (STAT3). These findings derived from experiments in hepatic cell lines LX-2 and Col-GFP, in which overexpression of PLIN5 was able to downregulate the signaling pathways SMAD2/3 and SNAIL activated previously by TGF-β1 treatment. Furthermore, TGF-β1-mediatedinduction of extracellular matrix proteins, such as collagen type I (COL1), Fibronectin, and α-smooth muscle actin (α-SMA), was suppressed by PLIN5. Moreover, STAT3, which is interrelated with TGF-β1 was already basally activated in the cell lines and inhibited by PLIN5 overexpression, leading to a further reduction in HSC activity shown by lowered α-SMA expression. This extension of the intervening mechanisms presents PLIN5 as a potent and pleiotropic target in HSC activation.
Highlights
Hepatic fibrosis, as a result of chronic liver injury, is a global medical burden with economic strains due to its high prevalence and potential complications [1]
The Western blot analysis of protein extracted from whole livers of around 35 weeks old wild type (WT) and Plin5−/− male mice, fed with normal chow, shows a clear enhancement of the extracellular matrix (ECM) proteins Fibronectin and COL1 as well as an enhancement of α-smooth muscle actin (α-SMA) in Plin5−/− mice compared to WT
The Western blot analysis of protein extracted from whole livers of around 35 weeks old WT and Plin5−/−male mice, fed with normal chow, shows a clear enhancement of the ECM proteins Fibronectin and COL1 as well as an enhancement of α-SMA in Plin5−/− mice compared to WT
Summary
As a result of chronic liver injury, is a global medical burden with economic strains due to its high prevalence and potential complications [1] Various triggers, such as alcohol abuse, hepatitis viruses, and metabolic disorders lead to an inflammatory and pro-fibrogenic process with an increased deposition of extracellular matrix (ECM) and overexpression of collagen type I (COL1) and Fibronectin [2], leading to tissue scarring. HSC are precursor mesenchymal cells of elusive origin which characteristically express the intermediate filaments Desmin and Vimentin [4,6] They are located in the sub-endothelial space between hepatocytes and sinusoidal endothelium, i.e., the space of Disse, and they represent about 10% of all resident cells of the liver. Understanding the reversal of activated HSC back into quiescence or better the prevention of activation of HSC in the first place is of great interest towards the development of therapeutic intervention options, in addition to the elimination of inflammation-provoking and damaging triggers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
