Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress
نویسندگان
چکیده
Chronic hypoxic stress induces epigenetic modifications mainly DNA methylation in cardiac fibroblasts, inactivating tumor suppressor genes (RASSF1A) and activating kinases (ERK1/2) leading to fibroblast proliferation fibrosis. The Ras/ERK signaling pathway is an intracellular signal transduction critically involved proliferation. RASSF1A functions through its effect on downstream ERK1/2. antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), decreases oxidative from chronic hypoxia, but effects these changes have not been fully explored. To test our hypothesis, we used in-vitro model: wild-type C57B6 male mice (WT) transgenic males with extra copy of human hEC-SOD (TG). studied animals were housed hypoxia (10% O 2 ) for 21 days. right ventricular tissue was fibrosis markers using RT-PCR Western blot analyses. Primary C57BL6 mouse culture study the model, RASSF-1 expression methylation, relation Our findings showed a significant increase markers: Collagen 1, alpha smooth muscle actin (ASMA), SNAIL, WT as compared TG group ( p < 0.05). enzymes (DNMT 1&3b) significantly increased 0.001). lower ERK1/2 higher Use SiRNA block gene murine led Methylation promoter region reduced (0.59 vs. 0.75, respectively). Based findings, can speculate that EC-SOD attenuates alleviate induced by hypoxia.
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ژورنال
عنوان ژورنال: Frontiers in Cardiovascular Medicine
سال: 2021
ISSN: ['2297-055X']
DOI: https://doi.org/10.3389/fcvm.2021.669975