The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice

<div>Suggested mechanism for the renal proximal convoluted tubule (PCT) injury in Hp 2-2 DN. The increased iron deposits in the PCT of the Hp 2-2 genotype generate a prooxidative environment in the kidney, leading to reduced renal expression of <i>α</i>-klotho and VDR proteins accompanied by an increased level of PCT injury. This subsequently interferes with vitamin D activation by 1-<i>α</i>-hydroxylase in the PCT, thereby increasing the kidney injury and the incidence of DN and its complications.</div>

Journal of Diabetes Research

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Figure 9

Figure 9: The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice 

Figure 9 | The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice 