Pendrin inhibition is associated with protective effect of prone positioning in a ventilator-induced lung injury mouse model

Pendrin (SLC26A4), a transmembrane anion exchanger, is upregulated in inflammatory airway diseases. In this study, we analyzed the role of pendrin expression in a ventilator-induced acute lung injury (VILI) animal model. VILI was induced in the supine or prone position by a high tidal volume (HTV) of 30 mL/kg for 5 h in pendrin wild-type (WT) and knockout (KO) 129SVEV mice. Pendrin inhibitor (YS-01) was intraperitoneally administered to modulate pendrin signaling. Lung injury parameters were assessed based on bronchoalveolar lavage fluid (BALF) analysis, inflammatory cytokine analysis by ELISA, and histopathological findings. Pendrin expression was determined by western blotting and transmission electron microscopy (TEM) using immunogold labeling methods. The degree of lung injury was significantly attenuated in pendrin-KO mice and pendrin-WT mice with YS-01 compared with pendrin-WT animals after HTV ventilation. Pendrin expression was down-regulated in pendrin-KO mice and pendrin-WT mice with YS-01 compared with pendrin-WT mice with VILI, as determined by western blotting and TEM-immunogold labeling. Prone positioning during ventilation attenuated lung inflammation and pendrin expression. Our results suggest that pendrin is critical in VILI and could be a novel target for modulating VILI. Prone positioning and pendrin inhibition in VILI may be effective in managing these conditions.