biostudies-literatureUnknown57Zhou M<h4>Background</h4>Skeletal muscle ischaemia-reperfusion (I/R) injury involves complex redox dysregulation with limited treatments. Although ferroptosis contributes to other organ I/R injuries, its role and regulation in skeletal muscle remain unclear. This study aimed to investigate the role and regulatory mechanism of ferroptosis in skeletal muscle I/R injury, specifically focusing on whether hypoxia-inducible factor 1 alpha (HIF1A) transcriptionally activates cyclin-dependent kinase inhibitor 1a (CDKN1A/p21) to drive this process.<h4>Methods</h4>We employed integrative transcriptomics and Cleavage Under Targets and Tagmentation (CUT&Tag, a chromatin mapping technique) sequencing in murine I/R models. Genetic inhibition (<i>Hif1a</i> siRNA) and pharmacological inhibition (LW6) were utiliJournal of orthopaedic translation101055https://www.ebi.ac.uk/biostudies/studies/S-EPMC12933464biostudies-literatureHIF1A transcriptionally activates CDKN1A to drive ferroptosis in skeletal muscle ischaemia-reperfusion injury.PMC12933464Zhou MLiu HPan XLiu JRui YMa YJin YWang KXue YWang PLi ZJia XWang YfalseHIF1A transcriptionally activates CDKN1A to drive ferroptosis in skeletal muscle ischaemia-reperfusion injury.<h4>Background</h4>Skeletal muscle ischaemia-reperfusion (I/R) injury involves complex redox dysregulation with limited treatments. Although ferroptosis contributes to other organ I/R injuries, its role and regulation in skeletal muscle remain unclear. This study aimed to investigate the role and regulatory mechanism of ferroptosis in skeletal muscle I/R injury, specifically focusing on whether hypoxia-inducible factor 1 alpha (HIF1A) transcriptionally activates cyclin-dependent kinase inhibitor 1a (CDKN1A/p21) to drive this process.<h4>Methods</h4>We employed integrative transcriptomics and Cleavage Under Targets and Tagmentation (CUT&Tag, a chromatin mapping technique) sequencing in murine I/R models. Genetic inhibition (<i>Hif1a</i> siRNA) and pharmacological inhibition (LW6) were utili2026-01-01T00:00:00Z2026 Mar2026-07-16T22:13:32.196Z2026-07-12T03:07:47.97ZS-EPMC129334644175729310.1016/j.jot.2026.101055