Abstract
Cells are subjected to endogenous [e.g., reactive oxygen species (ROS), replication stress] and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.
Highlights
Redox reactions are central to ensure correct cell function, allowing a dynamic transfer of electrons across different molecules (McCord, 2000)
Considering the body of work showing the deleterious effects of oxidative stress and DNA damage in the context of a variety of diseases on the one hand, and on the other hand, the impact of changes in the extracellular matrix (ECM) for disease onset and progression, this review aims to examine the potential links between oxidative stress/DNA damage and the ECM in the context of disease development
We explore studies showing how oxidative stress and DNA damage affect the synthesis of ECM molecules, focusing on the major, and best studied, glycoproteins of the ECM, namely collagens, fibronectin, and laminins (Hynes and Naba, 2012; Naba et al, 2016)
Summary
Redox reactions are central to ensure correct cell function, allowing a dynamic transfer of electrons across different molecules (McCord, 2000). Several diseases due to mutations in ECM components or proteins linking the ECM to the cell cytoskeleton have been shown to display increased oxidative stress and DNA damage in the affected tissues (Rando, 2002; Irwin et al, 2003; Rodriguez and Tarnopolsky, 2003; Millay et al, 2008; Shkryl et al, 2009; Menazza et al, 2010; de Oliveira et al, 2014; Sorato et al, 2014; Fontes-Oliveira et al, 2017; Gremminger et al, 2019; Kölbel et al, 2019; Moore et al, 2020) This is striking when considering the muscular dystrophies, but other examples exist.
Sign-in/Register to view highlights & summary 
Published Version (
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