The Iron-Klotho-VDR Axis Is a Major Determinant of Proximal Convoluted Tubule Injury in Haptoglobin 2-2 Genotype Diabetic Nephropathy Patients and Mice
المؤلفون المشاركون
Farber, Evgeny
Nakhoul, Nakhoul
Nakhoul, Farid
Ben-Itzhak, Ofer
Levy, Andrew P.
Dahan, Inbal
Thawho, Nadia
Asleh, Rabea
Li, Yan Chun
المصدر
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-12، 12ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-09-03
دولة النشر
مصر
عدد الصفحات
12
التخصصات الرئيسية
الملخص 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.
نمط استشهاد جمعية علماء النفس الأمريكية (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
نمط استشهاد الجمعية الأمريكية للغات الحديثة (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
نمط استشهاد الجمعية الطبية الأمريكية (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
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1183832
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر