Global Analysis of the Acetylome in Cisplatin-Induced Renal Fibrosis in C57BL/6 Mice

Background: Chronic kidney disease (CKD) is a major global health burden, and progressive renal fibrosis is a common end-stage pathway to renal failure. Lysine acetylation, as an important post-translational modification, has gradually become a reversible regulatory factor in renal injury and repair, but its systemic role in cisplatin-induced renal fibrosis remains unclear. Methods: Label-free quantitative proteomics and acetylome analyses were performed on the kidneys of C57BL/6 mice with cisplatin-induced renal fibrosis as well as the control groups (n = 4 per group). Subsequently, we conducted comprehensive bioinformatics analyses to identify key molecules that promote renal fibrosis. Results: We established proteomic and acetylomic profiles of lesions caused by cisplatin-induced renal fibrosis. Cisplatin-induced injury triggered extensive Kac remodeling, primarily involving pathways, such as the cell cycle, ATP-dependent chromatin remodeling, cell death, and extracellular matrix receptor interactions. We also identified significantly elevated lysine-96 acetylation of histone H2A (H2ac4 K96ac), whose abundance positively correlated to that of the acetyltransferase p300. This suggests that H2ac4 K96ac is a candidate epigenetic marker associated with cisplatin-induced renal fibrosis and warrants further investigation. Conclusion: This study provides comprehensive proteomic and acetylated proteomic data sets and maps for cisplatin-induced renal fibrosis. It is speculated that the H2ac4 K96ac histone acetylation site may represent a novel therapeutic target.