Epigenetic strategies for mitigating kidney fibrosis

Renal fibrosis is the irreversible pathological core of chronic kidney disease (CKD). Current treatments can slow disease progression, but cannot cure it. Epigenetic regulatory mechanisms provide new perspectives for understanding and intervening in this process. This review summarizes the core epigenetic regulatory networks involved in renal fibrosis, including DNA methylation, histone modification, and non-coding RNA regulation. First, abnormal DNA methylation can silence antifibrotic genes. Second, histone modifications dynamically regulate the chromatin state and affect the transcription of fibrosis-related genes. Moreover, ncRNAs regulate fibrosis signaling through complex networks. Preclinical studies support the potential value of DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, micro RNA-based strategies, N6-methyladenosine (m6A)-targeted approaches, natural products, and programmable epigenetic editing. Several barriers limit clinical translation. Future developments will depend on precision medicine. Optimizing targeted therapies, designing rational combination therapies, and establishing a strict, systematic long-term safety assessment system are key to translating epigenetic research results into effective treatments for renal fibrosis.