Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury

2021 ◽  
Author(s):  
Kuo Du ◽  
Seh Hoon Oh ◽  
Rajesh Kumar Dutta ◽  
Tianai Sun ◽  
Wen‐Hsuan Yang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Chronic Liver Injury

scholarly journals Liver fibrosis is driven by protease‐activated receptor‐1 expressed by hepatic stellate cells in experimental chronic liver injury

2020 ◽  
Vol 4 (5) ◽  
pp. 906-917
Author(s):  
Lauren G. Poole ◽  
Asmita Pant ◽  
Holly M. Cline‐Fedewa ◽  
Kurt J. Williams ◽  
Bryan L. Copple ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Protease Activated Receptor 1

275 ADAM10, ADAM17 AND MMP2 ACTIVITIES IN HEPATIC STELLATE CELLS ARE INVOLVED IN CX3CL1 PROCESSING AND CONTRIBUTE TO CHRONIC LIVER INJURY

2009 ◽  
Vol 50 ◽  
pp. S109
Author(s):  
K. Bourd-Boittin ◽  
L. Basset ◽  
D. Bonnier ◽  
A. L'Helgoualc'h ◽  
M. Samson ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Chronic Liver Injury

Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells

Gut ◽  
2019 ◽  
Vol 69 (5) ◽  
pp. 920-932 ◽  
Author(s):  
Alberto Martí-Rodrigo ◽  
Fernando Alegre ◽  
Ángela B Moragrega ◽  
Francisco García-García ◽  
Pablo Martí-Rodrigo ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Janus Kinase ◽  
In Vivo Models ◽  
Major Health Problem ◽  
Alcoholic Fatty Liver ◽  
Duct Ligation

ObjectiveLiver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation.DesignThe effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms.ResultsRPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism.ConclusionRPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV’s actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.

Sign in / Sign up

Export Citation Format

Share Document