Increased water intake decreases progression of polycystic kidney disease in the PCK rat

Shizuko Nagao, Kazuhiro Nishii, Makoto Katsuyama, Hiroki Kurahashi, Tohru Marunouchi, Hisahide Takahashi, Darren P. Wallace

研究成果: Article

162 引用 (Scopus)

抄録

Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.

元の言語English
ページ(範囲)2220-2227
ページ数8
ジャーナルJournal of the American Society of Nephrology
17
発行部数8
DOI
出版物ステータスPublished - 01-08-2006

Fingerprint

Polycystic Kidney Diseases
Extracellular Signal-Regulated MAP Kinases
Drinking
Kidney
Arginine Vasopressin
Vasopressin Receptors
Cysts
Mitogen-Activated Protein Kinase Kinases
Fluids and Secretions
Water
Diuresis
Proliferating Cell Nuclear Antigen
Drinking Water
Osmolar Concentration
Disease Progression
Phosphotransferases
Epithelial Cells
Body Weight
Urine
Glucose

All Science Journal Classification (ASJC) codes

  • Nephrology

これを引用

Nagao, Shizuko ; Nishii, Kazuhiro ; Katsuyama, Makoto ; Kurahashi, Hiroki ; Marunouchi, Tohru ; Takahashi, Hisahide ; Wallace, Darren P. / Increased water intake decreases progression of polycystic kidney disease in the PCK rat. :: Journal of the American Society of Nephrology. 2006 ; 巻 17, 番号 8. pp. 2220-2227.
@article{415779f4cbe14cde87c3bffb00953ad6,
title = "Increased water intake decreases progression of polycystic kidney disease in the PCK rat",
abstract = "Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5{\%} glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3{\%}), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0{\%}), B-Raf (15.4{\%}), phosphorylated ERK (38.1{\%}), and proliferating cell nuclear antigen-positive renal cells (61.7{\%}). High water intake reduced the kidney/body weight ratio 28.0{\%} and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.",
author = "Shizuko Nagao and Kazuhiro Nishii and Makoto Katsuyama and Hiroki Kurahashi and Tohru Marunouchi and Hisahide Takahashi and Wallace, {Darren P.}",
year = "2006",
month = "8",
day = "1",
doi = "10.1681/ASN.2006030251",
language = "English",
volume = "17",
pages = "2220--2227",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "8",

}

Increased water intake decreases progression of polycystic kidney disease in the PCK rat. / Nagao, Shizuko; Nishii, Kazuhiro; Katsuyama, Makoto; Kurahashi, Hiroki; Marunouchi, Tohru; Takahashi, Hisahide; Wallace, Darren P.

:: Journal of the American Society of Nephrology, 巻 17, 番号 8, 01.08.2006, p. 2220-2227.

研究成果: Article

TY - JOUR

T1 - Increased water intake decreases progression of polycystic kidney disease in the PCK rat

AU - Nagao, Shizuko

AU - Nishii, Kazuhiro

AU - Katsuyama, Makoto

AU - Kurahashi, Hiroki

AU - Marunouchi, Tohru

AU - Takahashi, Hisahide

AU - Wallace, Darren P.

PY - 2006/8/1

Y1 - 2006/8/1

N2 - Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.

AB - Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.

UR - http://www.scopus.com/inward/record.url?scp=33746566597&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746566597&partnerID=8YFLogxK

U2 - 10.1681/ASN.2006030251

DO - 10.1681/ASN.2006030251

M3 - Article

C2 - 16807403

AN - SCOPUS:33746566597

VL - 17

SP - 2220

EP - 2227

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 8

ER -