We have located links that may give you full text access.
Targeting Endothelial Erk1/2-Akt Axis as a Regeneration Strategy to Bypass Fibrosis during Chronic Liver Injury in Mice.
Molecular Therapy 2018 August 25
Liver sinusoidal endothelial cells (LSECs) have great capacity for liver regeneration, and this capacity can easily switch to profibrotic phenotype, which is still poorly understood. In this study, we elucidated a potential target in LSECs for regenerative treatment that can bypass fibrosis during chronic liver injury. Proregenerative LSECs can be transformed to profibrotic phenotype after 4 weeks of carbon tetrachloride administration or 10 days of bile duct ligation. This phenotypic alternation of LSECs was mediated by extracellular regulated protein kinases 1 and 2 (Erk1/2)-Akt axis switch in LSECs during chronic liver injury; Erk1/2 was normally associated with maintenance of the LSEC proregenerative phenotype, inhibiting hepatic stellate cell (HSC) activation and promoting tissue repair by enhancing nitric oxide (NO)/reactive oxygen species (ROS) ratio and increasing expression of hepatic growth factor (HGF) and Wingless-type MMTV integration site family member 2 (Wnt2). Alternatively, Akt induced LSEC profibrotic phenotype, which mainly stimulated HSC activation and concomitant senescence by reducing NO/ROS ratio and decreasing HGF/Wnt2 expression. LSEC-targeted adenovirus or drug particle to promote Erk1/2 activity can alleviate liver fibrosis, accelerate fibrosis resolution, and enhance liver regeneration. This study demonstrated that the Erk1/2-Akt axis acted as a switch to regulate the proregenerative and profibrotic phenotypes of LSECs, and targeted therapy promoted liver regeneration while bypassing fibrosis, providing clues for a more effective treatment of liver diseases.
Full text links
Related Resources
Trending Papers
Advances in Clinical Cardiology 2023: A Summary of Key Clinical Trials.Advances in Therapy 2024 May 15
Nutrition in the intensive care unit: from the acute phase to beyond.Intensive Care Medicine 2024 May 22
The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.Cardiac Failure Review 2024
Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.Cochrane Database of Systematic Reviews 2024 May 22
Bronchiectasis management in adults: state of the art and future directions.European Respiratory Journal 2024 May 24
Drug Therapy for Acute and Chronic Heart Failure with Preserved Ejection Fraction with Hypertension: A State-of-the-Art Review.American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions 2024 April 5
Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.Biomedicines 2024 April 31
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app