Células estrelladas hepáticas y estrés oxidativo

Abstract

RESUMENLa fibrosis hepática ocurre en la lesión hepática crónica y se caracteriza por la producción excesiva y el depósito de componentes de la matriz extracelular (MEC), fundamentalmente de colágeno de tipo I. Las células estralladas hepáticas (CEH) son las responsables de la producción excesiva de matriz extracelular durante la fibrosis. La activación de las CEH, constituye el paso fundamental del desarrollo de la fibrosis hepática y está mediada por citoquinas específicas y especies reactivas de oxígeno (ERO) que liberan los hepatocitos dañados, las células de Kupffer y las CEH activadas. Aunque las CEH permanecen normalmente en estado quiescente, se activan en respuesta a los factores que promueven la lesión hepática y proliferan y generan matriz. Un rasgo fundamental de la activación de las CEH es la producción incontrolada de colágeno de tipo I con una escasa degradación. El colágeno es una proteína heterotrimérica que se compone de dos cadenas α1 y una cadena α2, formando una triple hélice. El inicio de la activación de las células estrelladas se debe en gran medida a una estimulación paracrina, mientras que la perpetuación de dicho estado activado implica regulación tanto autocrina como paracrina. Esta revisión trata del papel del estrés oxidativo sobre la activación de las CEH.Palabras clave: Células estrelladas hepáticas. Fibrosis. Matriz extracelular. Especies reactivas de oxígeno. ABSTRACTHepatic fibrosis is a wound-healing response that takes place during chronic liver injury and is characterized by excessive production and deposition of extracellular matrix (ECM) components, mainly collagen type I. Hepatic stellate cells (HSC) are responsible for the excessive production of scar tissue during liver fibrosis. Activation of HSC, the main step in the development of hepatic fibrosis, is mediated by specific cytokines and reactive oxygen species (ROS) released by damaged hepatocytes and/or activated Kupffer cells and HSC. While HSC usually remain quiescent, in response to factors promoting liver injury they undergo activation and become highly proliferative and fibrogenic. Indeed a key feature of HSC activation is uncontrolled production of collagen type I with very little degradation. Collagen is a heterotrimeric protein composed of two α1 chains and one α2 chain forming a triple helix structure. Initiation of stellate cell activation is largely due to paracrine stimulation, whereas the perpetuation of such activated state involves autocrine as well as paracrine loops. This review focuses on the role of oxidant stress on the activation of stellate cells.

The Identification of Core Gene Expression Signature in Hepatocellular Carcinoma

“…Overexpression of MMP2 seemed strikingly associated with HCC because MMP2 in the tumor is mainly responsible for the fibrogenesis [ 25 ]. As reported, hepatic stellate cells, acting as main connective tissue cells in the liver, could be activated by oxidative stress and then produce extracellular matrix which is essential for normal growth and differentiation of cells after liver damage [ 26 ]. Our result suggests that oxidative stress in HCC not only directly affects the progression of HCC, but also interacts with other events to modulate HCC.…”

The Role of Autophagy and NLRP3 Inflammasome in Liver Fibrosis

“…Reactive oxygen species (ROS) are chemically reactive molecules produced during oxygen-related reactions. When the liver is attacked by harmful stimulations, hepatocytes, Kupffer cells, and HSCs themselves will produce large amounts of ROS [33,34], which react directly with intracellular lipids, proteins, and DNA, furtherly causing cell damage and death. Moreover, ROS can also activate HSCs through lipid peroxidation on the cell surface, leading to liver fibrosis.…”

Oxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical

“…Furthermore, ROS can specifically activate signaling pathways in HSC and LSEC, promoting fibrogenesis and increasing vascular tone. Particularly, in HSC, it has been suggested that ROS can trigger c-Jun N-terminal kinase (JNK), NFκB, and TGF-β signaling pathways, increasing the expression of collagen and other ECM components as well as pro-inflammatory mediators [ 48 , 49 , 50 , 51 ]. However, LSEC are probably the most sensitive liver cell type to oxidative stress.…”