Abstract
Various mechanisms, including inflammation, oxidative stress, and apoptosis, are involved in the transition from acute kidney injury to chronic kidney disease (AKI-to-CKD). In this study, we aimed to determine the pathway linking acute injury and fibrosis under static magnetic fields (SMFs). Human tubular epithelial cells (hTECs) were cultured on SMF platforms (119 mT; outward vs. inward direction) for 3 days, followed by treatment with adenine and p38 mitogen-activated protein kinase (MAPK) inhibitor to verify the role of MAPK pathway. In-vivo, mice were orally administered adenine (2mg/mouse/day) for 14 days to induce tubular injury, and p38 MAPK inhibitor (iP38, 10mg/kg) was injected intraperitoneally to evaluate its therapeutic effect. Inward SMF exposure significantly increased phospho-p38 (pp38) expression compared to outward SMFs. p38 MAPK inhibition reduced G1/S arrest and oxidative stress, apoptosis, and expression of fibrosis markers under inward SMFs. Additionally, iP38 treatment alleviated inflammation and fibrosis in adenine-induced tubular nephropathy (AITN). This study revealed that SMF-related AKI-to-CKD transition progresses with the direction of SMFs affecting the severity of injury, whereas p38 MAPK inhibition attenuates SMF-induced kidney injury and prevents fibrosis.
Keywords:
AKI-to-CKD; Cell cycle; Mitogen-activated protein pathway; Static magnetic field.