Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis

Josepha Lasky, Luis A. Ortiz, Boihoang Tonthat, Gary W. Hoyle, Miriam Corti, Grace Athas, Giuseppe Lungarella, Arnold Brody, Mitchell Friedman

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF- β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin- resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGFβ1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number2 19-2
StatePublished - Aug 1998
Externally publishedYes

Fingerprint

Connective Tissue Growth Factor
Fibrosis
Lung
Messenger RNA
Fibroblasts
Bleomycin
Transforming Growth Factors
indium-bleomycin
Response Elements
Inbred C57BL Mouse
Mitogens
Connective Tissue
Lung Diseases
Genes

Keywords

  • Collagen
  • Mice
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Lasky, J., Ortiz, L. A., Tonthat, B., Hoyle, G. W., Corti, M., Athas, G., ... Friedman, M. (1998). Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis. American Journal of Physiology - Lung Cellular and Molecular Physiology, 275(2 19-2).

Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis. / Lasky, Josepha; Ortiz, Luis A.; Tonthat, Boihoang; Hoyle, Gary W.; Corti, Miriam; Athas, Grace; Lungarella, Giuseppe; Brody, Arnold; Friedman, Mitchell.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 275, No. 2 19-2, 08.1998.

Research output: Contribution to journalArticle

Lasky, J, Ortiz, LA, Tonthat, B, Hoyle, GW, Corti, M, Athas, G, Lungarella, G, Brody, A & Friedman, M 1998, 'Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 275, no. 2 19-2.
Lasky, Josepha ; Ortiz, Luis A. ; Tonthat, Boihoang ; Hoyle, Gary W. ; Corti, Miriam ; Athas, Grace ; Lungarella, Giuseppe ; Brody, Arnold ; Friedman, Mitchell. / Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1998 ; Vol. 275, No. 2 19-2.
@article{04735623aa454978ae645e465d31a643,
title = "Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis",
abstract = "Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF- β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin- resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGFβ1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.",
keywords = "Collagen, Mice, Transforming growth factor-β1",
author = "Josepha Lasky and Ortiz, {Luis A.} and Boihoang Tonthat and Hoyle, {Gary W.} and Miriam Corti and Grace Athas and Giuseppe Lungarella and Arnold Brody and Mitchell Friedman",
year = "1998",
month = "8",
language = "English (US)",
volume = "275",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "2 19-2",

}

TY - JOUR

T1 - Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis

AU - Lasky, Josepha

AU - Ortiz, Luis A.

AU - Tonthat, Boihoang

AU - Hoyle, Gary W.

AU - Corti, Miriam

AU - Athas, Grace

AU - Lungarella, Giuseppe

AU - Brody, Arnold

AU - Friedman, Mitchell

PY - 1998/8

Y1 - 1998/8

N2 - Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF- β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin- resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGFβ1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

AB - Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF- β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin- resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGFβ1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

KW - Collagen

KW - Mice

KW - Transforming growth factor-β1

UR - http://www.scopus.com/inward/record.url?scp=0031845816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031845816&partnerID=8YFLogxK

M3 - Article

VL - 275

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 2 19-2

ER -