Hepatic Myofibroblasts: A Heterogeneous and Redox-Modulated Cell Population in Liver Fibrogenesis

Area of Science:

• Hepatology
• Cell Biology
• Oxidative Stress Research

Background:

• Hepatic myofibroblasts (MFs) are central to liver fibrogenesis and fibrosis progression in chronic liver disease (CLD).
• MF activation and pro-fibrogenic responses are significantly influenced by oxidative stress and reactive oxygen species (ROS).
• These cellular responses are often sustained by mediators that increase intracellular ROS generation.

Purpose of the Study:

• To review the role of MFs in CLD fibrogenesis across various etiologies.
• To elucidate the direct and indirect roles of ROS and oxidative stress in regulating MF phenotypes.
• To highlight the complex modulation of ROS during CLD progression.

Main Methods:

• Literature review focusing on hepatic myofibroblasts, oxidative stress, and reactive oxygen species in CLD.
• Analysis of the interplay between cellular mediators and ROS in fibrogenic pathways.
• Discussion of factors influencing cellular responses to ROS, including concentration and microenvironment.

Main Results:

• MFs exhibit common pro-fibrogenic responses elicited or sustained by oxidative stress and ROS.
• ROS and oxidative stress are critical regulators of MF phenotypic plasticity in CLD.
• The extracellular microenvironment and cellular state significantly impact ROS-mediated MF behavior.

Conclusions:

• Oxidative stress and ROS play a pivotal role in MF-driven liver fibrosis.
• Targeting ROS modulation pathways may offer therapeutic strategies for CLD.
• The complexity of ROS signaling in CLD necessitates a nuanced understanding for effective intervention.