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Pathogenic mechanisms for parathyroid hyperplasia

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1 Pathogenic mechanisms for parathyroid hyperplasia
A.S. Dusso, T. Sato, M.V. Arcidiacono, D. Alvarez-Hernandez, J. Yang, I. Gonzalez-Suarez, Y. Tominaga, E. Slatopolsky  Kidney International  Volume 70, Pages S8-S11 (July 2006) DOI: /sj.ki Copyright © 2006 International Society of Nephrology Terms and Conditions

2 Figure 1 The severity of parathyroid hyperplasia associates inversely with the resistance to calcitriol actions. In experimental SH in rats, the enlargement of the parathyroid glands (parathyroid gland area) from week 2 to week 4 after the onset of KD by 5/6 NX and a high P intake, correlates directly with increased parathyroid TGFα content and reduced VDR levels (immunohistochemical TGFα and VDR quantification). Kidney International  , S8-S11DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions

3 Figure 2 TGFα activation of the EGFR dictates the severity of parathyroid hyperplasia and the reduction of VDR content. In experimental SH, anti-EGFR therapy with EGFR-TKI, from week 2 to week 4 after the onset of KD by 5/6 NX and a high P intake prevents parathyroid TGFα self-induction and the reduction in parathyroid VDR content (imunohistochemical TGFα and VDR quantification, Means±s.e.m.; *P<0.05 and **P<0.01, respectively). Kidney International  , S8-S11DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions

4 Figure 3 Model for TGFα/EGFR induction of aggressive hyperplasia and vitamin D resistance. TGFα/EGFR induction of LIP expression causes aggressive growth through enhancement of cyclin D1 oncogenic signature and vitamin D resistance through reducing VDR gene expression. Kidney International  , S8-S11DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions

5 Figure 4 Enhanced LIP content in nodular human parathyroid glands. Western blot analysis of LIP content in whole-cell extracts (30 μg of total protein) from human parathyroid glands from patients with diffuse (Diffuse) and nodular (Nodular) SH, and parathyroid adenomas (Adenoma). Kidney International  , S8-S11DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions


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