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Increased Bone Morphogenetic Protein Signaling in the Cutaneous Vasculature of Patients with Calciphylaxis.

Abstract：

BACKGROUND:The objective of this study was to investigate the role of bone morphogenetic protein (BMP) signal transduction in the pathogenesis of calciphylaxis. METHODS:Skin biopsy specimens were obtained from 18 patients with, and 12 patients without, calciphylaxis. Tissue sections were stained with antibodies directed against BMP effector proteins phosphorylated-SMAD (p-SMAD) 1/5/9, inhibitor of DNA 1 (Id1), inhibitor of DNA 3 (Id3), and Runx2. The intensity of staining was scored semi-quantitatively as strong versus weak or absent. RESULTS:Of the 18 patients with calciphylaxis (mean age: 59 ± 8 years), 9 were women and 15 had end-stage renal disease. Of the 12 control patients (mean age: 57 ± 10 years), 8 were women and 8 had end-stage renal disease. Strong staining for p-SMAD 1/5/9 was detected in blood vessels from all calciphylaxis patients. In 1 patient with calciphylaxis, strong staining for p-SMAD 1/5/9 was detected in a blood vessel that did not have evidence of calcification. Id1 and Id3 immunoreactivity was detected in blood vessels from all 12 patients with calciphylaxis that were tested. Runx2 staining was detected in all 6 patients with calciphylaxis who were tested. p-SMAD 1/5/9 immunoreactivity was weak or absent in blood vessels of 10 of the 12 control samples. CONCLUSIONS:The BMP signal transduction pathway is activated in the cutaneous vasculature of calciphylaxis patients. The ability to detect p-SMAD 1/5/9, Id1, and Id3 in cutaneous vasculature may assist in the diagnosis of calciphylaxis. As BMP signaling inhibitors become available, this pathway may serve as a future therapeutic target for calciphylaxis.

journal_name

Am J Nephrol

journal_title

American journal of nephrology

authors

Nigwekar SU,Jiramongkolchai P,Wunderer F,Bloch E,Ichinose R,Nazarian RM,Thadhani RI,Malhotra R,Bloch DB

doi

10.1159/000484418

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

429-438

issue

5

eissn

0250-8095

issn

1421-9670

pii

000484418

journal_volume

46

pub_type

杂志文章

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