Grant: Operating Grant

A common feature of several lung diseases is extensive damage to alveoli. Acute lung injury (ALI) and its more devastating form, acute respiratory distress syndrome (ARDS), secondary to pneumonia, sepsis or trauma, for example, are characterized by severe injury to the alveolar epithelium, leading to lung oedema and respiratory failure. With a mortality rate of about 30%, ARDS is a common cause of mortality in hospital intensive care units. It has been established that alveolar regeneration is crucial for rapid recovery from ALI/ARDS, and it is clear that a better understanding of the alveolar repair mechanisms is necessary for the development of novel therapeutic strategies to improve survival in ARDS patients. Interestingly, our results show that proteins transporting K+ ions, called K+ channels, play a key role in the control of alveolar repair processes. Our main goal is to better understand the mechanisms of alveolar regeneration and, in particular, the role of K+ channels in repair processes, using cellular and animal models. In a first step, we will further study the role of K+ channels in cell migration and proliferation processes, crucial components of alveolar repair. Our second objective is to clarify the mechanisms and intracellular signals whereby K+ channels control alveolar repair. Our third objective is to explore the function of K+ channels in alveolar repair and secondary resolution of lung oedema in a mouse model of lung injury. In summary, our project aims to demonstrate that K+ channels are key elements of alveolar repair and could be identified as a promising strategy for the resolution of alveolar injury and secondary lung oedema in ARDS.