Alterations in cell cycle and MAPK pathway contribute to transition from SMF-associated acute kidney injury to fibrosis: Field direction matters

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 MAPK inhibitor to verify the role of MAP-kinase pathway. We orally administered 2 mg of adenine to mice daily for 14 days (adenine-induced tubular nephropathy; AITN). Phospho-p38 was significantly elevated in hTECs cultured under inward SMFs compared with that cultured under outward SMFs. Inhibition of p38 MAPK reduced G1/S arrest and oxidative stress, exerted anti-apoptotic effects, and downregulated the expression of fibrosis markers under inward SMFs. Deposition of F4/80-positive cells, IL-17R, p53, and p38 was significantly increased in AITN mice. p38 MAPK inhibition under inward SMFs led to a decrease in fibronectin expression in adenine-treated hTECs. 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.