Dexamethasone activates expression of the PDGF-α receptor and induces lung fibroblast proliferation

G. Sakuntala Warshamana, Sylvia Martinez, Joseph A. Lasky, Miriam Corti, Arnold R. Brody

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understand the mechanisms through which CSs control cell proliferation, we have carried out experiments to test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiescent cells in 1% serum or in serum- free media proliferate significantly in response to the addition of 10-7 to 10-9 M Dex. Increases as high as fourfold in cell numbers were recorded for the RLFs after 48 h in culture. A polyclonal antibody to the AB isoform of human platelet-derived growth factor (PDGF) blocked the proliferative response. As expected, the fibroblasts produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-α receptors (PDGF-Rα), the receptor type necessary for binding the AA isoform. Accordingly, we determined that Dex upregulated PDGF-Rα mRNA and protein. Therefore, we can postulate that Dex- induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-Rα.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number4 18-4
StatePublished - Apr 1998
Externally publishedYes

Fingerprint

Platelet-Derived Growth Factor Receptors
Dexamethasone
Fibroblasts
Platelet-Derived Growth Factor
Lung
Adrenal Cortex Hormones
Protein Isoforms
Interstitial Lung Diseases
Serum-Free Culture Media
Anti-Inflammatory Agents
Asthma
Cell Count
Cell Proliferation
Messenger RNA
Antibodies
Growth
Serum

Keywords

  • Anti-platelet-derived growth factor
  • Platelet-derived growth factor isoforms
  • Platelet-derived growth factor-α receptor

ASJC Scopus subject areas

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

Cite this

Dexamethasone activates expression of the PDGF-α receptor and induces lung fibroblast proliferation. / Warshamana, G. Sakuntala; Martinez, Sylvia; Lasky, Joseph A.; Corti, Miriam; Brody, Arnold R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 274, No. 4 18-4, 04.1998.

Research output: Contribution to journalArticle

Warshamana, G. Sakuntala ; Martinez, Sylvia ; Lasky, Joseph A. ; Corti, Miriam ; Brody, Arnold R. / Dexamethasone activates expression of the PDGF-α receptor and induces lung fibroblast proliferation. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1998 ; Vol. 274, No. 4 18-4.
@article{56270ae15566463ea3a64c4a3113e960,
title = "Dexamethasone activates expression of the PDGF-α receptor and induces lung fibroblast proliferation",
abstract = "Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understand the mechanisms through which CSs control cell proliferation, we have carried out experiments to test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiescent cells in 1{\%} serum or in serum- free media proliferate significantly in response to the addition of 10-7 to 10-9 M Dex. Increases as high as fourfold in cell numbers were recorded for the RLFs after 48 h in culture. A polyclonal antibody to the AB isoform of human platelet-derived growth factor (PDGF) blocked the proliferative response. As expected, the fibroblasts produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-α receptors (PDGF-Rα), the receptor type necessary for binding the AA isoform. Accordingly, we determined that Dex upregulated PDGF-Rα mRNA and protein. Therefore, we can postulate that Dex- induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-Rα.",
keywords = "Anti-platelet-derived growth factor, Platelet-derived growth factor isoforms, Platelet-derived growth factor-α receptor",
author = "Warshamana, {G. Sakuntala} and Sylvia Martinez and Lasky, {Joseph A.} and Miriam Corti and Brody, {Arnold R.}",
year = "1998",
month = "4",
language = "English (US)",
volume = "274",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "4 18-4",

}

TY - JOUR

T1 - Dexamethasone activates expression of the PDGF-α receptor and induces lung fibroblast proliferation

AU - Warshamana, G. Sakuntala

AU - Martinez, Sylvia

AU - Lasky, Joseph A.

AU - Corti, Miriam

AU - Brody, Arnold R.

PY - 1998/4

Y1 - 1998/4

N2 - Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understand the mechanisms through which CSs control cell proliferation, we have carried out experiments to test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiescent cells in 1% serum or in serum- free media proliferate significantly in response to the addition of 10-7 to 10-9 M Dex. Increases as high as fourfold in cell numbers were recorded for the RLFs after 48 h in culture. A polyclonal antibody to the AB isoform of human platelet-derived growth factor (PDGF) blocked the proliferative response. As expected, the fibroblasts produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-α receptors (PDGF-Rα), the receptor type necessary for binding the AA isoform. Accordingly, we determined that Dex upregulated PDGF-Rα mRNA and protein. Therefore, we can postulate that Dex- induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-Rα.

AB - Corticosteroids (CSs) are commonly used for anti-inflammatory therapy in asthma and in interstitial lung diseases. In attempting to understand the mechanisms through which CSs control cell proliferation, we have carried out experiments to test the effects of dexamethasone (Dex) on the growth of lung fibroblasts. Using mouse 3T3 fibroblasts as well as early-passage rat lung fibroblasts (RLFs), we show that the quiescent cells in 1% serum or in serum- free media proliferate significantly in response to the addition of 10-7 to 10-9 M Dex. Increases as high as fourfold in cell numbers were recorded for the RLFs after 48 h in culture. A polyclonal antibody to the AB isoform of human platelet-derived growth factor (PDGF) blocked the proliferative response. As expected, the fibroblasts produced primarily PDGF-A chain, and the RLFs exhibited few PDGF-α receptors (PDGF-Rα), the receptor type necessary for binding the AA isoform. Accordingly, we determined that Dex upregulated PDGF-Rα mRNA and protein. Therefore, we can postulate that Dex- induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-Rα.

KW - Anti-platelet-derived growth factor

KW - Platelet-derived growth factor isoforms

KW - Platelet-derived growth factor-α receptor

UR - http://www.scopus.com/inward/record.url?scp=0031978792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031978792&partnerID=8YFLogxK

M3 - Article

C2 - 9575867

AN - SCOPUS:0031978792

VL - 274

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 4 18-4

ER -