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

IF 4.5 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2026-10-05 eCollection Date: 2026-10-16 DOI:10.1016/j.isci.2026.117627

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

{"title":"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","doi":"10.1016/j.isci.2026.117627","DOIUrl":null,"url":null,"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 (KATP) 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 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. 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.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117627"},"PeriodicalIF":4.5000,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673107/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.isci.2026.117627","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/10/16 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

磺酰脲受体1缺乏通过激活上皮细胞中的PARP1减轻急性肺损伤。

急性肺损伤（ALI）是一种高死亡率的危重疾病，其发病机制尚未完全阐明。在这项研究中，我们研究了磺酰脲受体1 (SUR1)， atp敏感钾（KATP）通道的调节亚基，在ALI的进展。我们观察到脓毒症相关性ALI患者的支气管肺泡灌洗液（BALF）以及ALI小鼠模型的BALF和肺组织中SUR1蛋白水平升高。基因缺失的SUR1，而不是Kir6.2 （KATP通道的成孔亚基），显著减轻了盲肠结扎和穿刺（CLP）或脂多糖（LPS）气管内灌注引起的ALI。在机制上，SUR1与聚adp核糖聚合酶1 （PARP1）相互作用，损害DNA损伤修复，促进支气管上皮细胞凋亡和NF-κB（核因子κB）活化。值得注意的是，临床批准的SUR1抑制剂格列本脲通过破坏SUR1- parp1的相互作用，至少在一定程度上显著缓解了ALI。我们的研究结果确定SUR1是一个新的治疗靶点，并强调了格列本脲作为ALI治疗药物的潜在用途。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.