Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

Makoto Mizutani, Yasuhiko Ito, Masashi Mizuno, Hayato Nishimura, Yasuhiro Suzuki, Ryohei Hattori, Yoshihisa Matsukawa, Masaki Imai, Noelynn Oliver, Roel Goldschmeding, Jan Aten, Raymond T. Krediet, Yukio Yuzawa, Seiichi Matsuo

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Abstract

Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-β1 stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-β1-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF- β1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume298
Issue number3
DOIs
Publication statusPublished - 01-03-2010

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Connective Tissue Growth Factor
Peritoneal Dialysis
Peritoneal Fibrosis
Dialysis Solutions
Ultrafiltration
Messenger RNA
Peritoneum
Membranes
In Situ Hybridization
Renal Insufficiency
Real-Time Polymerase Chain Reaction
Creatinine
Proteins
Epithelium
Fibroblasts
Biomarkers
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Mizutani, Makoto ; Ito, Yasuhiko ; Mizuno, Masashi ; Nishimura, Hayato ; Suzuki, Yasuhiro ; Hattori, Ryohei ; Matsukawa, Yoshihisa ; Imai, Masaki ; Oliver, Noelynn ; Goldschmeding, Roel ; Aten, Jan ; Krediet, Raymond T. ; Yuzawa, Yukio ; Matsuo, Seiichi. / Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. In: American Journal of Physiology - Renal Physiology. 2010 ; Vol. 298, No. 3.
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abstract = "Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-β1 stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-β1-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF- β1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.",
author = "Makoto Mizutani and Yasuhiko Ito and Masashi Mizuno and Hayato Nishimura and Yasuhiro Suzuki and Ryohei Hattori and Yoshihisa Matsukawa and Masaki Imai and Noelynn Oliver and Roel Goldschmeding and Jan Aten and Krediet, {Raymond T.} and Yukio Yuzawa and Seiichi Matsuo",
year = "2010",
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Mizutani, M, Ito, Y, Mizuno, M, Nishimura, H, Suzuki, Y, Hattori, R, Matsukawa, Y, Imai, M, Oliver, N, Goldschmeding, R, Aten, J, Krediet, RT, Yuzawa, Y & Matsuo, S 2010, 'Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate', American Journal of Physiology - Renal Physiology, vol. 298, no. 3. https://doi.org/10.1152/ajprenal.00368.2009

Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. / Mizutani, Makoto; Ito, Yasuhiko; Mizuno, Masashi; Nishimura, Hayato; Suzuki, Yasuhiro; Hattori, Ryohei; Matsukawa, Yoshihisa; Imai, Masaki; Oliver, Noelynn; Goldschmeding, Roel; Aten, Jan; Krediet, Raymond T.; Yuzawa, Yukio; Matsuo, Seiichi.

In: American Journal of Physiology - Renal Physiology, Vol. 298, No. 3, 01.03.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

AU - Mizutani, Makoto

AU - Ito, Yasuhiko

AU - Mizuno, Masashi

AU - Nishimura, Hayato

AU - Suzuki, Yasuhiro

AU - Hattori, Ryohei

AU - Matsukawa, Yoshihisa

AU - Imai, Masaki

AU - Oliver, Noelynn

AU - Goldschmeding, Roel

AU - Aten, Jan

AU - Krediet, Raymond T.

AU - Yuzawa, Yukio

AU - Matsuo, Seiichi

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-β1 stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-β1-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF- β1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.

AB - Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-β1 stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-β1-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF- β1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.

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U2 - 10.1152/ajprenal.00368.2009

DO - 10.1152/ajprenal.00368.2009

M3 - Article

VL - 298

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1931-857X

IS - 3

ER -