TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000354785
  • Gene Name:FN1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB01656
  • Drug Name:Roflumilast
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:pulmonary fibrosis
  • Tissue:cell line GM06114

Other information

  • Title:A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro
  • Journal:Pulmonary Pharmacology & Therapeutics
  • Published:2010
  • PubMed ID:20226872
  • Abstract:The PDE4 inhibitor roflumilast mitigates bleomycin-induced lung fibrotic remodeling in rodents. In the current study it was explored whether roflumilast N-oxide, the active metabolite of roflumilast influences functions of cultured lung fibroblasts. Cells of the human foetal lung fibroblast strain GM06114 were stimulated with TNF-alpha (5 ng ml(-1)) and cell surface ICAM-1 and eotaxin release were assessed. [methyl-(3)H] thymidine incorporation was measured following stimulation with bFGF (10 ng ml(-1)). alpha-Smooth muscle actin (protein), CTGF (mRNA) and fibronectin (mRNA) were determined secondary to TGFbeta1 (1 ng ml(-1)). In the presence of PGE(2) (1 nM), roflumilast N-oxide reduced TNF-alpha-induced ICAM-1 and eotaxin by about 70% and >90% with half-maximum inhibition at 0.9 nM and 0.5 nM, respectively. Roflumilast N-oxide also attenuated [methyl-(3)H] thymidine incorporation secondary to bFGF by about 75% with half-maximum inhibition at 0.7 nM when cells were co-incubated with IL-1beta (10 pg ml(-1)). In the presence of this cytokine roflumilast N-oxide (1 microM) diminished TGFbeta1-induced expression of alpha-smooth muscle actin and transcripts of CTGF and fibronectin. In addition, IL-1beta up-regulated PDE4 activity in the lung fibroblasts. Taken together, these findings indicate that roflumilast N-oxide directly targets human lung fibroblasts, which may at least partially explain the efficacy of roflumilast to mitigate a pulmonary fibrotic response in vivo.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3