Dissecting the role of TRPC6-channels in bleomycin-induced pulmonary fibrosis

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 β) 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. C lassical T ransient R eceptor P otential 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.