%0 Journal Article %A Christopher Lambers %A Michael Roth %A Elisabeth Hofbauer %A Venzel Petkov %A Lutz-Henning Block %T Anti-remodeling potencies of the soluble guanylate cyclase activator BAY 41-2272 in human lung fibroblasts %D 2014 %J European Respiratory Journal %P 3423 %V 44 %N Suppl 58 %X Idiopathic pulmonary fibrosis (IPF) is typically a disease of the elderly and associated with poor prognosis. The hallmark of IPF is a diffuse tissue remodeling which results in major structural changes including mesenchymal cell hyperplasia and increased interstitial extracellular matrix (ECM) deposition mainly mediated by transforming growth factor (TGF) beta. Current evidence suggests important roles for local proliferation and differentiation of resident fibroblasts.We investigated the effect of the soluble Guanylate Cyclase (sGC) activator BAY 412272 on TGF induced ECM gene transcription and proliferation.Human lung fibroblasts were treated with TGF-beta (+/-) BAY 41 2272, Forskolin (FSK) and vehicle. mRNA transcription was measured by RT-PCR for Collagen type 1 (COL1), Fibronectin (FN), alpha smooth muscle actin (aSMA) and beta-Catenin. Proliferation was measured by cell count. All experiments were performed in triplicates.Stimulation of the cells with TGF led to a significant increase of mRNA transcription of Fibronectin (6.1 fold), Collagen type I (12.3 fold), a-SMA (3.9 fold;) and Catenin (3.6 fold), while pre-treatment with BAY 41-2272 resulted in a dose dependent significant reduction for COL1, FN, Catenin and a-SMA.TGF significantly increased cell proliferation after 72 hours. In contrast, the addition of BAY 41-2272 reversed this effect completely.These findings suggest that TGF driven ECM composition and cell proliferation can be modified by activation of soluble Guanylyl Cyclase (sGC). The demonstrated pharmacological effect of BAY 41-2272 proposes a new mode of action of the compound to prevent pulmonary remodeling. %U