beta-Thujaplicin Mobilizes Renal Tubular Iron to alleviate Diabetic Kidney Disease and hemolysis exacerbated kidney fibrosis
Diabetic kidney disease is a life-threatening complication of diabetes milieu. Iron metabolism has been shown to participate in the pathogenesis of DKD, while the mechanism and clinical intervention have not been fully interrogated. Here we employed a unilateral nephrectomy combined DKD mice model to demonstrate a distinct iron metabolic program in the kidney from DKD mice compared to controls. Specifically, although there was no alteration of total kidney iron content, a clear iron deposition was observed in the proximal tubules of the kidney from DKD mice vs. control. The aberrant iron deposition was correlated with fibrotic markers, suggesting an underlying link between iron and renal fibrosis in DKD. Importantly, an iron ionophore---beta-Thujaplicin, effectively mobilized iron from the tubules and significantly mitigated the kidney fibrosis in DKD mice. Transcriptome analysis suggested that beta-Thujaplicin restrained TGF-beta signaling to control fibrosis.