The transferrin a signaling pathway mediates uranium-induced hematopoietic dysfunction

This study was designed to explore the toxic effects of Transferrin a(tfa)-mediated uranium exposure on the hematopoietic system.

Zebrafish embryos were subjected to uranium nitrate solutions at concentrations of 50, 100, 250, and 500 μg/L for a defined period, followed by sample collection. The impact of uranium on hematopoietic system development in zebrafish was evaluated through hemoglobin staining, qRT-PCR, and in situ hybridization. RNA-Seq was utilized to detect differentially expressed genes (DEGs) in embryos exposed to 100 μg/L uranium, with subsequent bioinformatics analysis to confirm these DEGs. Furthermore, blood samples from patients with hematological disorders and impaired hematopoietic function were collected, and RNA-Seq was applied to identify DEGs.

Uranium exposure in zebrafish embryos led to reduced hemoglobin expression, with key transcription factors for primitive and definitive hematopoiesis being significantly downregulated at 100 μg/L uranium exposure. Overexpression of tfa resulted in a marked increase in hemoglobin content and upregulation of GATA1, a key factor in primitive hematopoiesis. Patients with hematopoietic dysfunction exhibited abnormalities in the tfa signaling pathway.

tfa plays a role in mediating the inhibitory effects of uranium on hematopoietic function.