Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism

Masahide Mizobuchi, Hiroaki Ogata, Ikuji Hatamura, Fumihiko Koiwa, Fumie Saji, Kazuhiro Shiizaki, Shigeo Negi, Eriko Kinugasa, Akira Ooshima, Shozo Koshikawa, Tadao Akizawa

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background. Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the pathogenesis of the disorder is still obscure. The present study examined the expressions of bone-associated factors in calcified arteries in subtotally nephrectomized rats with severe secondary hyperparathyroidism (SHPT). Methods. Seven-week-old male Sprague - Dawley rats were divided into five groups as follows: sham-operated rats that received a normal diet [0.8% of phosphorus (P), 1.1% of calcium (Ca)] (Sham), sham-operated rats that received a high-phosphorus and low-calcium (HPLCa) diet (1.2% P, 0.4% Ca) (Sham+HPLCa), 5/6 nephrectomized rats that received a normal diet as the uraemic control group (Nx), and 5/6 nephrectomized rats that received a HPLCa diet to induce the development of SHPT (Nx+HPLCa), and 5/6 nephrectomized and parathyroidectomized rats that received a HPLCa diet (Nx+PTx+HPLCa). The feeding period of each group was 10 weeks. The rats were then sacrificed and their serum was examined. The upper part of the abdominal aorta was used to investigate the expression of mRNAs of core-binding factor alpha-1 (Cbfa1) and sodium-dependent phosphate cotransporter (Pit-1) by real-time reverse transcriptase polymerase chain reaction (real-time PCR) analysis. The lower part was examined for calcification by von Kossa staining. Results. Serum P level and Ca × P products increased significantly in the Nx+HPLCa group compared with those of any other groups. Severe hyperparathyroidism was also observed in the Nx+HPLCa group. Vascular calcification (medial layer) was observed in the Nx+HPLCa group only. There was a significant increase in Cbfa1 and Pit-1 mRNA expression levels in the aorta of the Nx+HPLCa group compared with that of any other groups. Conclusions. These results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.

Original languageEnglish (US)
Pages (from-to)911-916
Number of pages6
JournalNephrology Dialysis Transplantation
Volume21
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

Secondary Hyperparathyroidism
Up-Regulation
Phosphorus
Arteries
Calcium
Vascular Calcification
Diet
Chronic Kidney Failure
core binding factor alpha
Sodium-Phosphate Cotransporter Proteins
Messenger RNA
Hyperparathyroidism
Abdominal Aorta
Reverse Transcriptase Polymerase Chain Reaction
Serum
Sprague Dawley Rats
Aorta
Real-Time Polymerase Chain Reaction
Cause of Death
Cardiovascular Diseases

Keywords

  • Core-binding factor alpha-1 (Cbfa1)
  • Hyperphosphataemia
  • Secondary hyperparathyroidism (SHPT)
  • Sodium-dependent phosphate cotransporter (Pit-1)
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism. / Mizobuchi, Masahide; Ogata, Hiroaki; Hatamura, Ikuji; Koiwa, Fumihiko; Saji, Fumie; Shiizaki, Kazuhiro; Negi, Shigeo; Kinugasa, Eriko; Ooshima, Akira; Koshikawa, Shozo; Akizawa, Tadao.

In: Nephrology Dialysis Transplantation, Vol. 21, No. 4, 04.2006, p. 911-916.

Research output: Contribution to journalArticle

Mizobuchi, M, Ogata, H, Hatamura, I, Koiwa, F, Saji, F, Shiizaki, K, Negi, S, Kinugasa, E, Ooshima, A, Koshikawa, S & Akizawa, T 2006, 'Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism', Nephrology Dialysis Transplantation, vol. 21, no. 4, pp. 911-916. https://doi.org/10.1093/ndt/gfk008
Mizobuchi, Masahide ; Ogata, Hiroaki ; Hatamura, Ikuji ; Koiwa, Fumihiko ; Saji, Fumie ; Shiizaki, Kazuhiro ; Negi, Shigeo ; Kinugasa, Eriko ; Ooshima, Akira ; Koshikawa, Shozo ; Akizawa, Tadao. / Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism. In: Nephrology Dialysis Transplantation. 2006 ; Vol. 21, No. 4. pp. 911-916.
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TY - JOUR

T1 - Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism

AU - Mizobuchi, Masahide

AU - Ogata, Hiroaki

AU - Hatamura, Ikuji

AU - Koiwa, Fumihiko

AU - Saji, Fumie

AU - Shiizaki, Kazuhiro

AU - Negi, Shigeo

AU - Kinugasa, Eriko

AU - Ooshima, Akira

AU - Koshikawa, Shozo

AU - Akizawa, Tadao

PY - 2006/4

Y1 - 2006/4

N2 - Background. Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the pathogenesis of the disorder is still obscure. The present study examined the expressions of bone-associated factors in calcified arteries in subtotally nephrectomized rats with severe secondary hyperparathyroidism (SHPT). Methods. Seven-week-old male Sprague - Dawley rats were divided into five groups as follows: sham-operated rats that received a normal diet [0.8% of phosphorus (P), 1.1% of calcium (Ca)] (Sham), sham-operated rats that received a high-phosphorus and low-calcium (HPLCa) diet (1.2% P, 0.4% Ca) (Sham+HPLCa), 5/6 nephrectomized rats that received a normal diet as the uraemic control group (Nx), and 5/6 nephrectomized rats that received a HPLCa diet to induce the development of SHPT (Nx+HPLCa), and 5/6 nephrectomized and parathyroidectomized rats that received a HPLCa diet (Nx+PTx+HPLCa). The feeding period of each group was 10 weeks. The rats were then sacrificed and their serum was examined. The upper part of the abdominal aorta was used to investigate the expression of mRNAs of core-binding factor alpha-1 (Cbfa1) and sodium-dependent phosphate cotransporter (Pit-1) by real-time reverse transcriptase polymerase chain reaction (real-time PCR) analysis. The lower part was examined for calcification by von Kossa staining. Results. Serum P level and Ca × P products increased significantly in the Nx+HPLCa group compared with those of any other groups. Severe hyperparathyroidism was also observed in the Nx+HPLCa group. Vascular calcification (medial layer) was observed in the Nx+HPLCa group only. There was a significant increase in Cbfa1 and Pit-1 mRNA expression levels in the aorta of the Nx+HPLCa group compared with that of any other groups. Conclusions. These results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.

AB - Background. Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the pathogenesis of the disorder is still obscure. The present study examined the expressions of bone-associated factors in calcified arteries in subtotally nephrectomized rats with severe secondary hyperparathyroidism (SHPT). Methods. Seven-week-old male Sprague - Dawley rats were divided into five groups as follows: sham-operated rats that received a normal diet [0.8% of phosphorus (P), 1.1% of calcium (Ca)] (Sham), sham-operated rats that received a high-phosphorus and low-calcium (HPLCa) diet (1.2% P, 0.4% Ca) (Sham+HPLCa), 5/6 nephrectomized rats that received a normal diet as the uraemic control group (Nx), and 5/6 nephrectomized rats that received a HPLCa diet to induce the development of SHPT (Nx+HPLCa), and 5/6 nephrectomized and parathyroidectomized rats that received a HPLCa diet (Nx+PTx+HPLCa). The feeding period of each group was 10 weeks. The rats were then sacrificed and their serum was examined. The upper part of the abdominal aorta was used to investigate the expression of mRNAs of core-binding factor alpha-1 (Cbfa1) and sodium-dependent phosphate cotransporter (Pit-1) by real-time reverse transcriptase polymerase chain reaction (real-time PCR) analysis. The lower part was examined for calcification by von Kossa staining. Results. Serum P level and Ca × P products increased significantly in the Nx+HPLCa group compared with those of any other groups. Severe hyperparathyroidism was also observed in the Nx+HPLCa group. Vascular calcification (medial layer) was observed in the Nx+HPLCa group only. There was a significant increase in Cbfa1 and Pit-1 mRNA expression levels in the aorta of the Nx+HPLCa group compared with that of any other groups. Conclusions. These results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.

KW - Core-binding factor alpha-1 (Cbfa1)

KW - Hyperphosphataemia

KW - Secondary hyperparathyroidism (SHPT)

KW - Sodium-dependent phosphate cotransporter (Pit-1)

KW - Vascular calcification

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U2 - 10.1093/ndt/gfk008

DO - 10.1093/ndt/gfk008

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VL - 21

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JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

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ER -