Sulfonylurea receptor 1 deficiency alleviates acute lung injury by activating PARP1 in epithelial cells

In this study we investigated sulfonylurea receptor 1 (SUR1), the regulatory subunit of ATP-sensitive potassium (KATP) channels, in the progression of ALI. We observed elevated SUR1 protein levels in the bronchial alveolar lavage fluid (BALF) of patients with sepsis-associated ALI, as well as in BALF and lung tissues of ALI mouse models.

Genetic deletion of SUR1, but not Kir6.2 (the pore-forming subunit of KATP channels), significantly alleviated ALI induced by cecal ligation and puncture (CLP) or by lipopolysaccharide (LPS) intratracheal instillation. Mechanistically, SUR1 interacted with poly (ADP-ribose) polymerase 1 (PARP1), impairing DNA damage repair and promoting apoptosis and NF-κB (nuclear factor kappa B) activation in bronchial epithelial cells.