As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systemati...As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systematically expounds the coordinated mechanism of the dual axes of succinate/H3K9ac andα-ketoglutarate(α-KG)/TET enzymes:Succinate activates regeneration-related genes by regulating histone acetylation(H3K9ac),whileα-KG relieves the epigenetic repression of the Wnt pathway through TET-mediated DNA demethylation.The dynamic balance between the two maintains epigenetic plasticity.Multi-omics integration strategies(such as Gaussian graphical models and deep learning frameworks)and single-cell epigenetic tracking technologies(such as spatial metabolomics)have revealed the regulation of metabolite gradients on cellular heterogeneity and the immune microenvironment.The coordinated application of metabolite precursor supplementation(such as NAD precursors)and dynamic monitoring systems(such as isotope tracing and artifi cial intelligence models)has promoted the shift of metabolic medicine from the“static replacement”paradigm to the“dynamic reshaping”paradigm.However,technical bottlenecks(such as insuffi cient multimodal integration)and clinical translation pitfalls(such as challenges in standardized production)still need to be overcome.In the future,through the development of“metabolism-immunity”co-regulatory strategies and intelligent closed-loop systems,it is expected to achieve precise interventions for kidney regeneration and disease treatment.展开更多
基金funded by Medical Science Research Project of Hebei(No.20220364).
文摘As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systematically expounds the coordinated mechanism of the dual axes of succinate/H3K9ac andα-ketoglutarate(α-KG)/TET enzymes:Succinate activates regeneration-related genes by regulating histone acetylation(H3K9ac),whileα-KG relieves the epigenetic repression of the Wnt pathway through TET-mediated DNA demethylation.The dynamic balance between the two maintains epigenetic plasticity.Multi-omics integration strategies(such as Gaussian graphical models and deep learning frameworks)and single-cell epigenetic tracking technologies(such as spatial metabolomics)have revealed the regulation of metabolite gradients on cellular heterogeneity and the immune microenvironment.The coordinated application of metabolite precursor supplementation(such as NAD precursors)and dynamic monitoring systems(such as isotope tracing and artifi cial intelligence models)has promoted the shift of metabolic medicine from the“static replacement”paradigm to the“dynamic reshaping”paradigm.However,technical bottlenecks(such as insuffi cient multimodal integration)and clinical translation pitfalls(such as challenges in standardized production)still need to be overcome.In the future,through the development of“metabolism-immunity”co-regulatory strategies and intelligent closed-loop systems,it is expected to achieve precise interventions for kidney regeneration and disease treatment.
