P10 - Role of TRP channels for pulmonary metal toxicity and alveolar bioenergetics
Acquired or inherited defects of epithelial transport leads to severe respiratory diseases such as cystic fibrosis, pulmonary oedema and impaired protection of the lung from pathogens or pollutants. However, the molecular identity of transport proteins responsible for ion homeostasis in the lung, has remained a mystery. We have previously shown that the channel-kinases TRPM6 and TRPM7 control the transcellular epithelial transport of divalent cations, including Ca2+, Mg2+ and Zn2. TRPM6 is specifically expressed in AT2 cells, but not in other alveolar cells. Genetic disruption of Trpm6 in mice is associated with impaired secretion of pulmonary surfactant and development of lung emphysema as a hallmark of chronic obstructive pulmonary disease (COPD). Therefore, our project aims at deciphering the mechanisms by which mineral homeostasis in the lung determines the metabolic activity of AT2 cells and maintains their regenerative potential, and to investigate whether dietary Mg2+ and TRPM6/M7 small-molecule agonists are able to prevent, delay or even reverse lung emphysema in a mouse model of chronic exposure to cigarette smoke.
Dr. Ali Önder YildirimInstitute of Lung Biology and Disease (ILBD) Comprehensive Pneumology Center (CPC) +49-89-3187-4037 |