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

Authors

Xiaojuan Yin, Qiaoqiao Zhu, Li Zhao, Wenqing Ma, Liying Wang, Huiling Li, Chao Wang, Yipin Wang, Lin Xu, Haijun Zhang, Xuerong Wang, Wenbin Huang

Published in

iScience. Volume 29. Issue 10. Pages 117627. Oct 16, 2026. Epub Oct 05, 2026.

Abstract

Acute lung injury (ALI) is a critical disease with high mortality, yet its mechanisms remain incompletely elucidated. In this study, we investigated sulfonylurea receptor 1 (SUR1), the regulatory subunit of ATP-sensitive potassium (K_ATP) channels, in the progression of ALI. We observed elevated SUR1 protein levels in the bronchoalveolar 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 K_ATP 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. Notably, glibenclamide, a clinically approved SUR1 inhibitor, significantly alleviated ALI, at least in part, by disrupting the SUR1-PARP1 interaction. Our findings identify SUR1 as a new therapeutic target and highlight the potential repurposing of glibenclamide as a therapeutic drug in ALI.

PMID:
42891087
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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