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Dissecting the Role of TRPC6 Channels in Pulmonary Fibrosis
Author(s) -
Dietrich Alexander,
Hofmann Katharina,
Koenigshoff Melanie,
Gudermann Thomas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.863.24
Subject(s) - trpc6 , myofibroblast , pulmonary fibrosis , bleomycin , transdifferentiation , lung , fibrosis , fibrocyte , fibroblast , cancer research , pathology , microbiology and biotechnology , medicine , biology , chemistry , stem cell , receptor , cell culture , transient receptor potential channel , genetics , chemotherapy
Pulmonary fibrosis (PF) is a progressive lung disease ultimately leading to death. Current evidence indicates that fibrosis is driven by activated alveolar epithelial cells (AECs) induced by drugs like bleomycin. AEC produce profibrotic mediators (TGF‐β and ATII) which initiate aberrant epithelial‐fibroblast crosstalk and induce the formation of fibroblast and myofibroblast 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 6 (TRPC6) is an unselective cation channel highly expressed in different lung tissues. TRPC6 might contribute to pulmonary fibrosis because the channel plays an important role in myofibroblast transdifferentiation and wound healing in cardiac fibroblasts (Davis et al. (2012). Dev. Cell 23, 705‐715). Moreover, TRPC6 is responsible for increased vascular permeability in lungs (Weissmann et al. (2012). Nat. Commun. 3, 649) which might help circulating fibrocytes to migrate to injured areas. To study a potential role of TRPC6 in PF we analyze function, histology, gene and protein expression in WT and TRPC6‐/‐ mouse lungs after bleomycin‐instillation. Results indicate that TRPC6‐deficient lungs expose a less severe pulmonary fibrosis than WT lungs. We now investigate primary alveolar epithelial cells and fibroblasts from bleomycin‐treated and untreated WT and TRPC6‐/‐ mice 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.