Source: International Congress 2014 – ILDs 3
Disease area: Interstitial lung diseases

Abstract

Pulmonary fibrosis (PF) is a progressive lung disease of unknown cause. Current evidence indicates that the fibrotic response is driven by abnormally activated alveolar epithelial cells (AECs) caused by epithelial injury. AEC produce profibrotic mediators (e.g transforming growth factor b) which initiate aberrant epithelial-fibroblast crosstalk and induce the formation of (myo)fibroblast foci through the proliferation of resident mesenchymal cells. Moreover, fibrocytes from the peripheral blood are attracted and migrate to the injured areas facilitated by an increased vascular permeability. Classical Transient Receptor Potential channel 6 (TRPC6) is an unselective cation channel highly expressed in different lung tissues. TRPC6 might contribute to pulmonary fibrosis since it is known that the channel plays an important role in myofibroblast transdifferentiation and wound healing in cardiac and dermal fibroblasts. Moreover, TRPC6 is responsible for increased vascular permeability in lungs which might help circulating fibrocytes to migrate to the injured areas. To study a potential role of TRPC6 in PF we analyze function, histology, gene and protein expression in WT and TRPC6-/- lungs after bleomycin-instillation. Initial results indicate that TRPC6-deficient lungs expose a less severe pulmonary fibrosis than WT lungs. In the future we will investigate primary alveolar epithelial cells and primary murine fibroblasts from bleomycin-treated and untreated WT and TRPC6-/- animals to understand molecular differences in cell functions induced by cation influx through TRPC6. Defining TRPC6 function in these cells will help to identify pharmacological targets for new therapeutic options in PF.

Rating:

Share or cite this content

Citations should be made in the following way:
K. Hofmann, V. Aumiller, O. Yildirim, T. Gudermann, M. Königshoff, A. Dietrich (Munich, Germany). Dissecting the role of TRPC6-channels in bleomycin-induced pulmonary fibrosis. Eur Respir J 2014; 44: Suppl. 58, 791

Member's Comments

No comment yet.

Related content which might interest you: Parenchymal cell populations involved in the development of fibrosis Source: International Congress 2014 – ILDs 4 Year: 2014 Assessment of telomere length in the combined pulmonary fibrosis and emphysema syndrome Source: International Congress 2014 – ILDs: diagnostic and prognostic investigations Year: 2014 Idiopathic pulmonary fibrosis is associated with a preferential alteration of kCO rather than of DLCO Source: International Congress 2014 – ILDs 6 Year: 2014 Sulforaphane attenuates lung fibrosis in bleomycin-induced pulmonary fibrosis via inhibition of TGF-beta/Smad signaling Source: International Congress 2014 – ILDs 4 Year: 2014 Dasatinib suppresses TGFbeta-induced epithelial mesenchymal transition and inhibits pulmonary fibrosis Source: International Congress 2014 – ILDs 1 Year: 2014 Predictors of efficacy of pirfenidone in idiopathic pulmonary fibrosis Source: International Congress 2014 – ILDs 4 Year: 2014 The role of Frizzled8 in idiopathic pulmonary fibrosis Source: International Congress 2014 – New and old players in fibrotic lung disease Year: 2014 Effect of pirfenidone on TGF-beta-induced pro-fibrotic effects in primary human lung cells derived from patients with idiopathic pulmonary fibrosis Source: International Congress 2014 – ILDs 2 Year: 2014 Platelet activation indices in patients with Idiopathic Pulmonary Fibrosis Source: International Congress 2014 – ILDs 5 Year: 2014 MiR-214-3p, a new fibromiR involved in the pathogenesis of idiopathic pulmonary fibrosis Source: International Congress 2014 – Pathogenetic mechanisms in pulmonary fibrosis Year: 2014 Safety and efficacy of pirfenidone in severe idiopathic pulmonary fibrosis Source: International Congress 2014 – ILDs 3 Year: 2014 LATE-BREAKING ABSTRACT: The effects and mechanism of adiponectin on inhibiting pulmonary fibrosis Source: International Congress 2014 – ILDs 1 Year: 2014 Surfactant protein B proforms as potential new biomarkers for idiopathic pulmonary fibrosis Source: International Congress 2014 – ILDs 2 Year: 2014 Pirfenidone and BIBF1120 regulate properties of myofibroblasts Source: International Congress 2014 – ILDs: pathogenesis and clinical features Year: 2014 Pirfenidone in idiopathic pulmonary fibrosis - description of a German cohort Source: International Congress 2014 – ILDs 4 Year: 2014 Analysis of candidate genes of phenotypic expression in idiopathic pulmonary fibrosis Source: International Congress 2014 – ILDs 5 Year: 2014 Elevated protein arginine methyltransferase 1 expression contributes to the pathogenesis of pulmonary fibrosis Source: International Congress 2014 – ILDs: pathogenesis and clinical features Year: 2014 The role of CCR2+CD4+T cells in lung fibrosis Source: International Congress 2014 – Pathogenetic mechanisms in pulmonary fibrosis Year: 2014 Pulmonary distribution and localization of pirfenidone in animal models of IPF by MS/MS Source: International Congress 2014 – ILDs 4 Year: 2014 Role of MUC1 in idiopathic pulmonary fibrosis Source: International Congress 2016 – ILD pathogenesis Year: 2016