Role And Intervention Of Anion Exchange Transporter Pendrin In Acute Lung Injury In Mice

Introduction:Airway dysfunction in patients with the Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) is definite by wall thickening with inflammation, extracellular matrix remodeling and epithelial denudation. Pendrin (SLC26A4), an anion exchanger found on airway epithelial cells, appears to contribute to airway inflammation and pathology. Its role in asthma and chonic obstructive pulmonary disease (COPD) have been revealed. To date, however, no study has focused on the pendrin changes in lungs with ALI/ARDS. Meanwhile, whether pendrin exsiting on alveoli is underdetermined. The aim of this study is to evaluate the role of pendrin in ALI/ARDS and to explore whether pendrin expression existing on alveolar cells.Methods:Lipopolysaccharide (LPS) intratracheally induced ALI C57BL/6 mice model. By RT-PCR and western blotting, analyse the expression of pendrin in lung. With administration of Methazolamide (5mg/kg) by subcutaneous injection every 12h after 1h of LPS insult, observe the changes of lung inflammatory parameters and pathology. Using a dual label immunofluorescence technique to determine the cellular distribution of pendrin in the lung. The observation time of the model and intervention was 48h. Statistical comparisons between groups of mice were made by two-tailed Student’s t-test. P< 0.05 was considered statistically significant.Results:Enhanced expression of the SLC26A4 gene and production of pendrin in lungs of LPS-induced ALI mice were confirmed. In comparison with vehicle-control mice, Methazolamide treatment mitigated lung inflammatory parameters and pathology. IL-6 and MCP-1 in lung tissues and BALF in Methazolamide-treated mice were statistically decreased. Methazolamide treatment had significant effect on the total protein concentration in the BALF and the lung wet to dry weight ratio. The percentage of macrophages in the BALF was increased. There was a low expression of pendrin in on ATII.Conclusions:Pendrin may involve pathological process of LPS-induced ALI. As a target, to inhibit the function of pendrin could be used to treat ALI. It is signalized that airway epithelial cell may be a valuable therapeutic target for discovering and developing new drugs and/or new therapeutic strategies for the treatment of ALI/ARDS. The expression of pendrin on the alveolar type II cells is confirmed, despite the function is undetermined.