Histone modification-mediated epigenetic regulation in AKI-to-CKD transition: a cell-type-specific perspective.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a multifaceted process that involves various pathological events such as injury to renal tubular epithelial cells (RTECs) and vascular endothelial cells, followed by cell cycle arrest, activation of inflammatory responses, capillary rarefaction, and tissue hypoxia. Histone modifications, as critical epigenetic regulators, orchestrate gene expression patterns that govern renal repair, immune response, and fibrotic remodeling during this transition. Despite some advancements, the specific mechanisms underlying the AKI to CKD transition remain incompletely understood. This manuscript reviews the role of histone modifications, including methylation, acetylation, lactylation, and crotonylation, in regulating gene expression and their impact on kidney injury repair, inflammation, and fibrosis. The kidney, as an organ with structural and functional heterogeneity, each cell type plays a unique role in the transition from AKI to CKD and exhibits distinct patterns of gene expression regulation. The study specifically examines how histone modifications affect different cell types involved in this transition, including renal tubular epithelial cells, immune cells, endothelial cells, fibroblasts, and podocytes. Our findings highlight the significant contributions of histone modification-driven mechanisms in the pathogenesis of CKD and suggest potential therapeutic strategies targeting histone modifiers. Despite existing challenges, targeted therapies based on histone modification mechanisms offer promising breakthroughs for preventing or mitigating the AKI to CKD transition.