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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 274 |
| Issue number | 4 18-4 |
| State | Published - Apr 1998 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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 -