Lung transplantation is an effective treatment for end-stage lung diseases.
However, ischemia-reperfusion (IR) is an inevitable process during lung transplant, which leads to primary graft dysfunction (PGD). , PGD is the major cause of early morbidity and mortality after lung transplantation. Pathological characteristics of IR and PGD mainly include neutrophil activation, release of pro-inflammatory cytokines, endothelial cell dysfunction, and disruption of the endothelial barrier, resulting in pulmonary edema and impaired pulmonary function. ,
Currently, there are no therapeutic agents clinically utilized to specifically prevent PGD. Thus, better understanding the mechanisms of lung ischemia-reperfusion injury (IRI) is paramount for the treatment of PGD.
Aquaporins (AQPs) are small, hydrophobic, integral membrane proteins that mediate water transport across the membranes in various systems.
The change of AQPs expression is associated with development of IR induced inflammation and edema in multiple organs, including brain, kidneys, retinal and testis tissues. Among 13 identified AQPs, AQP1 and AQP3-5 are expressed in the lung. AQP3 is expressed in the epithelial cells of the trachea and bronchi, facilitating water transport across the air space-capillary barrier. , AQP4 is detected in the basolateral membrane of the bronchial epithelium and is involved in transendothelial/transepithelial water permeability. AQP5 is expressed in the alveolar epithelium, participating in transcellular water absorption and secretion in airway. AQP1 is abundantly expressed in endothelial cells surrounding terminal bronchiole and alveolus and is the dominating route for water transition across the pulmonary microvascular endothelium. , A protective role of AQP1 was described in lung IRI induced by cardiopulmonary bypass. However, the role of AQP1 during lung IR was disputable, as studies have shown that AQP1 expression is upregulated or decreased in various IR lung injury models. Thus, further investigation is needed. Therefore, we hypothesis that AQP1 plays a role in the development of edema and inflammation during lung IRI. We are hoping to develop a new target for the improvement of PGD after lung transplant.