Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

作     者：Mengqi Zhu Sainan Min Xiangdi Mao Yuan Zhou Yan Zhang Wei Li Li Li Liling Wu Xin Cong Guangyan Yu Mengqi Zhu;Sainan Min;Xiangdi Mao;Yuan Zhou;Yan Zhang;Wei Li;Li Li;Liling Wu;Xin Cong;Guangyan Yu

作者机构：Department of Oral and Maxillofacial SurgeryPeking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Department of Physiology and PathophysiologyPeking University School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular SciencesMinistry of Educationand Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijingChina Department of Biomedical InformaticsPeking University School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular SciencesMinistry of EducationBeijingChina 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2022年第14卷第3期

页      面：321-333页

核心收录：

学科分类：1003[医学-口腔医学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.81974151 31972908 81991500 and 81991502) 

主　　题：Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis IgG 

摘      要：Immunoglobulin G4-related sialadenitis(IgG4-RS)is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully *** aim of this study was to explore the role and mechanism of interleukin-13(IL-13)in the cellular senescence during the progress of *** found that the expression of IL-13 and IL-13 receptorα1(IL-13Rα1)as well as the number of senescent cells were significantly higher in the submandibular glands(SMGs)of IgG4-RS ***-13 directly induced senescence as shown by the elevated activity of senescence-associatedβ-galactosidase(SA-β-gal),the decreased cell proliferation,and the upregulation of senescence markers(p53 and p16)and senescence-associated secretory phenotype(SASP)factors(IL-1βand IL-6)in SMG-C6 ***,IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6(p-STAT6)and mitochondrial-reactive oxygen species(mt ROS),while decreased the mitochondrial membrane potential,ATP level,and the expression and activity of superoxide dismutase 2(SOD2).Notably,the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger Mito ***,IL-13 increased the interaction between p-STAT6 and c AMP-response element binding protein(CREB)-binding protein(CBP)and decreased the transcriptional activity of CREB on *** together,our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.