The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice
Joint Authors
Farber, Evgeny
Nakhoul, Nakhoul
Nakhoul, Farid
Ben-Itzhak, Ofer
Levy, Andrew P.
Dahan, Inbal
Thawho, Nadia
Asleh, Rabea
Li, Yan Chun
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-09-03
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
The haptoglobin (Hp) genotype (1-1 and 2-2) is a major determinant of nephropathy progression in diabetes mellitus patients.
Hp 2-2 diabetic mice have impaired Hb clearance and increased iron deposits and oxidative stress in the proximal tubules (PCT), leading to increased renal injury.
However, the precise mechanism of the PCT injury in diabetic nephropathy (DN) remains elusive.
In the kidney, 1,25(OH)2D3 suppresses the inflammatory response to renal tubular injury and requires normal renal expression of the α-klotho protein.
In this study, we set out to test the hypothesis that the increased renal iron deposits in the PCT of Hp 2-2 DN affect the α-klotho-vitamin D receptor (VDR) axis and thereby exacerbates the PCT injury generated by the iron deposits.
Immunohistochemical analysis of human and mouse kidney biopsies along with western blot analysis showed that the increased iron deposits in the PCT of the Hp 2-2 genotype were accompanied with significantly decreased α-klotho and VDR renal expression but significantly increased 1-α-hydroxylase renal expression.
In conclusion, the iron-klotho-VDR axis is a major player in the mechanism contributing to iron-mediated PCT injury in diabetic Hp 2-2 mice and patients.
Targeting this axis may open the way for new ideas regarding the pathogenesis and treatment of DN.
American Psychological Association (APA)
Dahan, Inbal& Thawho, Nadia& Farber, Evgeny& Nakhoul, Nakhoul& Asleh, Rabea& Levy, Andrew P.…[et al.]. 2018. The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice. Journal of Diabetes Research،Vol. 2018, no. 2018, pp.1-12.
https://search.emarefa.net/detail/BIM-1183832
Modern Language Association (MLA)
Dahan, Inbal…[et al.]. The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice. Journal of Diabetes Research No. 2018 (2018), pp.1-12.
https://search.emarefa.net/detail/BIM-1183832
American Medical Association (AMA)
Dahan, Inbal& Thawho, Nadia& Farber, Evgeny& Nakhoul, Nakhoul& Asleh, Rabea& Levy, Andrew P.…[et al.]. The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice. Journal of Diabetes Research. 2018. Vol. 2018, no. 2018, pp.1-12.
https://search.emarefa.net/detail/BIM-1183832
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1183832