Rapamycin Inhibits Transforming Growth Factor beta1-Induced Fibrogenesis in Primary Human Lung Fibroblasts
Yonsei Medical Journal
;
: 437-444, 2013.
Article
in English
| WPRIM
| ID: wpr-89564
ABSTRACT
PURPOSE:
The present study was designed to determine whether rapamycin could inhibit transforming growth factor beta1 (TGF-beta1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. MATERIALS ANDMETHODS:
Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax. Growth arrested, synchronized fibroblasts were treated with TGF-beta1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay.RESULTS:
Rapamycin significantly reduced TGF-beta1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-beta1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-beta1-mediated fibrogenic response in primary human lung fibroblasts.CONCLUSION:
These results indicate that rapamycin effectively suppresses TGF-beta1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pulmonary Fibrosis
/
Signal Transduction
/
Cells, Cultured
/
Fibronectins
/
Sirolimus
/
Collagen Type III
/
Transforming Growth Factor beta1
/
TOR Serine-Threonine Kinases
/
Fibroblasts
/
Lung
Limits:
Humans
Language:
English
Journal:
Yonsei Medical Journal
Year:
2013
Type:
Article
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