Field direction of static magnetic fields influences kidney fibrosis progression through MAPK signaling and cell cycle alteration

Sci Rep. 2025 Jul 10;15(1):24841. doi: 10.1038/s41598-025-09077-w.

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.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Adenine
  • Animals
  • Apoptosis / drug effects
  • Cell Cycle*
  • Disease Progression
  • Epithelial Cells / metabolism
  • Fibrosis
  • Humans
  • Kidney* / metabolism
  • Kidney* / pathology
  • MAP Kinase Signaling System*
  • Magnetic Fields* / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases
  • Adenine