Regulation of Mitochondria and Mitochondrial Oxygen Species by TGF-β

In patients with fibrosis, the imbalance of the manifestation of reactive oxygen species (ROS) and the body’s detoxifying abilities results in oxidative stress in the cytoplasm and mitochondria. Increased production of ROS can stimulate extracellular matrix synthesis, leading to persistent fibrosis. To determine how the addition of TGF-β affects mitochondria ROS production, RNA was isolated from human foreskin fibroblasts and quantitative polymerase chain reaction was used to examine changes in the levels of mRNA in the mitochondria and nucleus after the application of TGF-β. Western blot technique determined TGF-β’s effect on SIRT3, a post-transcriptional modifier that plays a key role in mitochondria ROS production, and Ac-MnSOD2, an enzyme that clears ROS; the levels of SIRT3 expression were relatively similar in the TGF-β-treated cells and the control group; however, Ac- MnSOD2 expression levels were elevated slightly in the TGF-β treated sample as compared to the control, suggesting reduced SIRT3 activities. Apigenin, a natural plant product and a SIRT3 activator, possesses the ability to reduce TGF-β-induced collagen and α-smooth muscle actin expression. TGF-β can induce mitochondrial complex III ROS generation, which promotes TGF-β mediated expression of fibrosis genes. Targeting mitochondria ROS production by activating SIRT3 may have clinical potential in fibrosis therapy.