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.