Key result
Heterozygous TfR1 deletion in mice attenuated renal fibrosis and reduced renal expression of ferritin, 4-hydroxynonenal, TGFβ-RI, and Smad2 following ureteral obstruction or streptozotocin.
Why the study?
Renal iron load and oxidative stress contribute to renal disease, but no studies have investigated the role of transferrin receptor 1 (TfR1) in the pathophysiology of renal fibrosis.
Does heterozygous TfR1 deletion prevent renal fibrosis in mouse models of obstructive nephropathy and diabetic kidney disease?
Does heterozygous TfR1 deletion prevent renal fibrosis in mouse models of obstructive nephropathy and diabetic kidney disease?
Heterozygous deletion of TfR1 attenuates renal fibrosis in mouse models of obstructive nephropathy and diabetic kidney disease, suggesting a role for TfR1 in renal fibrosis pathogenesis.
Renal fibrosis is the final pathological process common for several types of end-stage renal diseases, including obstructive nephropathy and diabetic kidney disease. Substantial renal iron loads and oxidative stress have been reported to contribute to the development of renal diseases. TfR1 (transferrin receptor 1) plays a crucial role in cellular iron transport. However, there are no studies investigating TfR1 in the pathophysiology of renal fibrosis. Here, we investigate the role of TfR1 in the development of renal fibrosis. Primarily, to ascertain an association of TfR1 in the pathophysiology of renal fibrosis, we induced unilateral ureteral obstruction in wild-type (WT) and heterozygous TfR1 deleted ( TfR1 +/− ) mice. TfR1 +/− mice exhibited attenuated renal fibrosis, along with reduced renal expression of ferritin and 4-hydroxynonenal as compared with WT mice after unilateral ureteral obstruction. In addition, renal expression of TGFβ-RI (transforming growth factor-β receptor I) and Smad2, downstream signaling of TGFβ-RI was attenuated in TfR1 +/− mice compared with WT mice after unilateral ureteral obstruction. Next, we investigated the role of TfR1 in the development of diabetic kidney disease. No difference was observed in blood glucose levels and urinary albumin:creatinine ratios between WT and TfR1 +/− diabetic mice after streptozotocin administration. In contrast, TfR1 +/− mice showed suppressed renal fibrosis, along with reduced renal expression of ferritin, 4-hydroxynonenal, TGFβ-RI, and Smad2 compared with WT mice after streptozotocin administration. These results suggest that TfR1 plays an important role in the development of renal fibrosis.
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Yasumura et al. (2019) studied Renal fibrosis. Heterozygous TfR1 deletion vs. Wild-type mice was evaluated on Renal fibrosis and expression of ferritin, 4-hydroxynonenal, TGFβ-RI, and Smad2. Heterozygous TfR1 deletion in mice attenuated renal fibrosis and reduced renal expression of ferritin, 4-hydroxynonenal, TGFβ-RI, and Smad2 following ureteral obstruction or streptozotocin.
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