Unknown

Dataset Information

0

Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation.


ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-?1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-?1, or the combination. Cells were pre-incubated (30?min) with either Treprostinil, forskolin, di-deoxyadenosine (DDA), or vehicle. Treprostinil time dependently activated cAMP thereby preventing PDGF-BB induced proliferation and TGF-?1 secretion. Cell counts indicated proliferation; ?-smooth muscle actin (?-SMA) indicted differentiation, and collagen type-1 or fibronectin deposition remodeling. Myo-fibroblast indicating ?-SMA expression was significantly reduced and its formation was altered by Treprostinil. Collagen type-I and fibronectin deposition were also reduced by Treprostinil. The effect of Treprostinil on collagen type-I deposition was cAMP sensitive as it was counteracted by DDA, while the effect on fibronectin was not cAMP mediated. Treprostinil antagonized the pro-fibrotic effects of both PDGF-BB and TGF-?1 in primary human lung fibroblasts. The data presented propose a therapeutic relevant anti-fibrotic effect of Treprostinil in IPF.

SUBMITTER: Lambers C 

PROVIDER: S-EPMC5773699 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

altmetric image

Publications

Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation.

Lambers Christopher C   Roth Michael M   Jaksch Peter P   Muraközy Gabriella G   Tamm Michael M   Klepetko Walter W   Ghanim Bahil B   Zhao Feng F  

Scientific reports 20180118 1


Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lun  ...[more]

Similar Datasets

2022-03-20 | GSE128618 | GEO
| S-EPMC5381689 | biostudies-literature
| S-EPMC10493503 | biostudies-literature
| S-EPMC9009985 | biostudies-literature
| S-EPMC3089559 | biostudies-literature
| S-EPMC9236907 | biostudies-literature
| S-EPMC4308848 | biostudies-literature
| S-EPMC3784246 | biostudies-literature
| S-EPMC4532446 | biostudies-literature
| S-EPMC3826988 | biostudies-literature