Abstract 14830: Cellular Iron Transport Protein, Transferrin Receptor 1 Plays an Important Role in the Pathophysiology of Chronic Kidney Disease

• Published in: Circulation (New York, N.Y.) Vol. 132; no. Suppl_3 Suppl 3; p. A14830
• Main Authors: Oboshi, Makiko, Naito, Yoshiro, Sawada, Hisashi, Iwasaku, Toshihiro, Okuhara, Yoshitaka, Morisawa, Daisuke, Eguchi, Akiyo, Nishimura, Koichi, Soyama, Yuko, Hirotani, Shinichi, Mano, Toshiaki, Ishihara, Masaharu, Tsujino, Takeshi, Masuyama, Tohru
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 10.11.2015
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.132.suppl_3.14830

BackgroundCellular iron transport protein, transferrin receptor 1 (TfR1) is required for the uptake of transferrin-bound iron into the cells. Several reports have shown that iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD); however, the role of TfR1 in the pathophysiology of CKD remains unknown. Herein, we investigate TfR1 in the experimental models of CKD.Methods and ResultsCKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. CKD rats showed proteinuria and tubular dilatation. Of note, TfR1 expression is increased in the remnant kidney along with increased iron accumulation, as compared with controls. To investigate the functional importance of TfR1 in the pathophysiology of CKD, we subjected to 5/6 nephrectomy in TfR1 hetero knockout mice. At 8weeks after 5/6 nephrectomy, systolic blood pressure was similar in TfR1 hetero knockout mice and wild-type (WT) littermates. In contrast, urinary albumin excretion, serum BUN, and creatinine levels were increased to a lesser extent in TfR1 hetero knockout mice compared with WT littermates. In addition, renal fibrosis was observed in the remnant kidney in WT mice, while the extent was attenuated in TfR1 hetero knockout mice. Consistent with these findings, increased renal gene expression of collagen type I and collagen type III were attenuated in TfR1 hetero knockout mice compared with WT littermates.ConclusionsThese results indicate that TfR1 plays a role in the pathophysiology of CKD. Understanding the role of TfR1 in the pathophysiology of CKD may lead to a novel therapeutic approach for CKD.