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Involvement of parathyroid hormone‐related protein in vascular calcification of chronic haemodialysis patients
Author(s) -
LIU FANG,
FU PING,
FAN WENXING,
GOU RONG,
HUANG YOUQUN,
QIU HONGYU,
ZHONG HUI,
HUANG SONGMIN
Publication year - 2012
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2012.01601.x
Subject(s) - parathyroid hormone related protein , medicine , calcification , runx2 , downregulation and upregulation , endocrinology , staining , parathyroid hormone , bone morphogenetic protein 2 , osteopontin , western blot , alkaline phosphatase , calcium , pathology , chemistry , biochemistry , enzyme , in vitro , gene
Aims: To investigate the role of parathyroid hormone‐related protein (PTHrP) in vascular calcification of patients with chronic hemodialysis. Methods: The inferior epigastric arteries were obtained from 23 patients on chronic haemodialysis and 16 patients with renal carcinoma as control. Haematoxylin‐eosin staining, elastic fibre staining, Alizarin Red calcium staining and immunohistochemical staining of PTHrP, bone morphogenetic protein‐2 (BMP‐2), Cbfa1/Runx2 were performed. Real‐time polymerase chain reaction (PCR) was used to examine mRNA expressions of PTHrP, BMP‐2 and Cbfa1/Runx2. Western blot and real‐time PCR were used to detect the effects of PTHrP‐siRNA and rh‐PTHrP‐1–34 on the expressions of PTHrP, BMP‐2 and Cbfa1/Runx2 in human aortic smooth muscle cells (HASMC). Alkaline phosphatase (ALP) activities and intracellular calcium content in HASMCs were assessed after treatment with 10 mmol/L β‐glycerol phosphoric acid for 48 h. Results: Vascular calcification was confirmed in 78.2% of patients on chronic haemodialysis, and the expressions of PTHrP, BMP‐2 and Cbfa1 in the arteries were significantly upregulated. PTHrP‐siRNA could downregulate the expression of PTHrP by 60%, BMP‐2 by 25% and Cbfa1 by 25% at 24 h ( P < 0.05). Exogenous rh‐PTHrP‐1–34 could upregulate the expressions of BMP‐2 and Cbfa1 by 1.37‐fold and 1.46‐fold, respectively, at 24 h in a time‐independent manner ( P < 0.05), which were attenuated by PTHrP‐siRNA. Moreover, it could promote intracellular calcium deposition and increase ALP activities, which were partially blocked by PTHrP‐siRNA (P < 0.05). Conclusions: Vascular calcification was common in patients with chronic haemodialysis, to which PTHrP might contribute by activating BMP‐2/ Cbfa1 signalling pathway.