Trimethylamine N-oxide mediated Y-box binding protein-1 nuclear translocation promotes cell cycle progression by directly downregulating Gadd45a expression in a cellular model of chronic kidney disease

YB-1 accumulated in the cytoplasm of HK-2 cells after treatment with 400 μM trimethylamine N-oxide (TMAO) for 30 minutes and 6 hours.

• RNA sequencing revealed differential expression of cell cycle checkpoint genes, including Gadd45a and cyclins, after TMAO treatment.
• Cell cycle progression was blocked at the G2/M checkpoint in HK-2 cells following TMAO exposure.
• In animal models, increased dietary TMAO resulted in progressive renal dysfunction and reduced YB-1 expression in the kidneys.
• YB-1 was shown to directly bind to the promoter region of Gadd45a, regulating its expression.
• YB-1 expression is negatively correlated with Gadd45a and Gadd45g, while positively correlated with Ccna2, Ccnb1, Ccne1, and Ccnf in chronic kidney disease.

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