Tissue-specific regulation of growth factors and clusterin by angiotensin II

Kee Hwan Yoo, Barbara A. Thornhill, Jennifer T. Wolstenholme, Robert L. Chevalier

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic responses of the heart and kidney to systemic hypertension. To determine whether these actions of ANG II are related to tissue-specific stimulation of growth factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or low-dose ANG II were normotensive with normal plasma aldosterone concentration, whereas rats receiving high-dose ANG II were hypertensive with increased plasma aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA (mRNA) for transforming growth factor-β1 (TGF-β1) and prepro-epidermal growth factor (EGF) was measured in liver, heart, and renal glomeruli and tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF-β1 expression in glomeruli, tubules, and heart, but not in liver, and increased EGF expression in renal tubules only. High-dose ANG II decreased clusterin expression in liver only. Fibrosis was induced by low- and high-dose ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively stimulates TGF- β1 mRNA in the heart and kidney, which may contribute to cardiac and renal interstitial fibrosis resulting from activation of the renin-angiotensin system independent of hypertension. By stimulating cellular proliferation, selective stimulation by ANG II of EGF in renal tubules may amplify the effects of TGF-β1. Suppression of clusterin expression in the liver of hypertensive rats may represent a specific response to high levels of circulating ANG II or a response to hypertensive injury.

Original languageEnglish
Pages (from-to)715-722
Number of pages8
JournalAmerican Journal of Hypertension
Volume11
Issue number6 I
DOIs
Publication statusPublished - 1998 Jun 1

Fingerprint

Clusterin
Angiotensin II
Intercellular Signaling Peptides and Proteins
Kidney
Transforming Growth Factors
Epidermal Growth Factor
Liver
Fibrosis
Aldosterone
Messenger RNA
Hypertension
Wounds and Injuries
Renin-Angiotensin System
Sprague Dawley Rats
Glycoproteins

Keywords

  • Angiotensin
  • Clusterin
  • Epidermal growth factor
  • Hypertension
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Tissue-specific regulation of growth factors and clusterin by angiotensin II. / Yoo, Kee Hwan; Thornhill, Barbara A.; Wolstenholme, Jennifer T.; Chevalier, Robert L.

In: American Journal of Hypertension, Vol. 11, No. 6 I, 01.06.1998, p. 715-722.

Research output: Contribution to journalArticle

Yoo, Kee Hwan ; Thornhill, Barbara A. ; Wolstenholme, Jennifer T. ; Chevalier, Robert L. / Tissue-specific regulation of growth factors and clusterin by angiotensin II. In: American Journal of Hypertension. 1998 ; Vol. 11, No. 6 I. pp. 715-722.
@article{ff85b9994be7497dac632a03ec85f163,
title = "Tissue-specific regulation of growth factors and clusterin by angiotensin II",
abstract = "Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic responses of the heart and kidney to systemic hypertension. To determine whether these actions of ANG II are related to tissue-specific stimulation of growth factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or low-dose ANG II were normotensive with normal plasma aldosterone concentration, whereas rats receiving high-dose ANG II were hypertensive with increased plasma aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA (mRNA) for transforming growth factor-β1 (TGF-β1) and prepro-epidermal growth factor (EGF) was measured in liver, heart, and renal glomeruli and tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF-β1 expression in glomeruli, tubules, and heart, but not in liver, and increased EGF expression in renal tubules only. High-dose ANG II decreased clusterin expression in liver only. Fibrosis was induced by low- and high-dose ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively stimulates TGF- β1 mRNA in the heart and kidney, which may contribute to cardiac and renal interstitial fibrosis resulting from activation of the renin-angiotensin system independent of hypertension. By stimulating cellular proliferation, selective stimulation by ANG II of EGF in renal tubules may amplify the effects of TGF-β1. Suppression of clusterin expression in the liver of hypertensive rats may represent a specific response to high levels of circulating ANG II or a response to hypertensive injury.",
keywords = "Angiotensin, Clusterin, Epidermal growth factor, Hypertension, Transforming growth factor-β",
author = "Yoo, {Kee Hwan} and Thornhill, {Barbara A.} and Wolstenholme, {Jennifer T.} and Chevalier, {Robert L.}",
year = "1998",
month = "6",
day = "1",
doi = "10.1016/S0895-7061(98)00018-1",
language = "English",
volume = "11",
pages = "715--722",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "6 I",

}

TY - JOUR

T1 - Tissue-specific regulation of growth factors and clusterin by angiotensin II

AU - Yoo, Kee Hwan

AU - Thornhill, Barbara A.

AU - Wolstenholme, Jennifer T.

AU - Chevalier, Robert L.

PY - 1998/6/1

Y1 - 1998/6/1

N2 - Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic responses of the heart and kidney to systemic hypertension. To determine whether these actions of ANG II are related to tissue-specific stimulation of growth factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or low-dose ANG II were normotensive with normal plasma aldosterone concentration, whereas rats receiving high-dose ANG II were hypertensive with increased plasma aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA (mRNA) for transforming growth factor-β1 (TGF-β1) and prepro-epidermal growth factor (EGF) was measured in liver, heart, and renal glomeruli and tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF-β1 expression in glomeruli, tubules, and heart, but not in liver, and increased EGF expression in renal tubules only. High-dose ANG II decreased clusterin expression in liver only. Fibrosis was induced by low- and high-dose ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively stimulates TGF- β1 mRNA in the heart and kidney, which may contribute to cardiac and renal interstitial fibrosis resulting from activation of the renin-angiotensin system independent of hypertension. By stimulating cellular proliferation, selective stimulation by ANG II of EGF in renal tubules may amplify the effects of TGF-β1. Suppression of clusterin expression in the liver of hypertensive rats may represent a specific response to high levels of circulating ANG II or a response to hypertensive injury.

AB - Angiotensin II (ANG II) has been implicated in the hypertrophic and fibrotic responses of the heart and kidney to systemic hypertension. To determine whether these actions of ANG II are related to tissue-specific stimulation of growth factors, we infused adult Sprague-Dawley rats with ANG II at 50 ng/min (low dose), 100 ng/min (high dose), or vehicle for 1 week. Rats receiving vehicle or low-dose ANG II were normotensive with normal plasma aldosterone concentration, whereas rats receiving high-dose ANG II were hypertensive with increased plasma aldosterone. Tissue fibrosis was quantified morphometrically, and messenger RNA (mRNA) for transforming growth factor-β1 (TGF-β1) and prepro-epidermal growth factor (EGF) was measured in liver, heart, and renal glomeruli and tubules. In addition, mRNA was determined for clusterin, a glycoprotein expressed in response to tissue injury. Compared to vehicle, low-dose ANG II increased TGF-β1 expression in glomeruli, tubules, and heart, but not in liver, and increased EGF expression in renal tubules only. High-dose ANG II decreased clusterin expression in liver only. Fibrosis was induced by low- and high-dose ANG II in kidney and heart, but not in liver. We conclude that ANG II selectively stimulates TGF- β1 mRNA in the heart and kidney, which may contribute to cardiac and renal interstitial fibrosis resulting from activation of the renin-angiotensin system independent of hypertension. By stimulating cellular proliferation, selective stimulation by ANG II of EGF in renal tubules may amplify the effects of TGF-β1. Suppression of clusterin expression in the liver of hypertensive rats may represent a specific response to high levels of circulating ANG II or a response to hypertensive injury.

KW - Angiotensin

KW - Clusterin

KW - Epidermal growth factor

KW - Hypertension

KW - Transforming growth factor-β

UR - http://www.scopus.com/inward/record.url?scp=0031839057&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031839057&partnerID=8YFLogxK

U2 - 10.1016/S0895-7061(98)00018-1

DO - 10.1016/S0895-7061(98)00018-1

M3 - Article

VL - 11

SP - 715

EP - 722

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 6 I

ER -