Figure 2.

Mutations in ECM components increase oxidative stress. Many diseases caused by mutations in ECM components or components that link ECM to the cytoskeleton have been associated with generation of excess ROS levels. The loss of collagen I, collagen VI, laminin α2, or dystrophin was shown to induce mitochondrial dysfunction, a major source of ROS. Additionally, high ROS levels due to either increased activity of monoamine oxidase A (MAO-A) or NADPH oxidase have also been associated with the loss of specific ECM or ECM-related components. Loss of laminin α2 or dystrophin leads to increased levels of ROS as a consequence of the activation of inflammatory cells. Dystrophin loss was also shown to promote changes in the activity of antioxidant pathways and ROS-induced DNA damage.