Seliciclib alleviates ulcerative colitis by inhibiting ferroptosis and improving intestinal inflammation

作者全名："Song, Ya; Song, Qian; Tan, Fangyan; Wang, Yanhui; Li, Chuanfei; Liao, Shengtao; Yu, Keqi; Mei, Zhechuan; Lv, Lin"

作者地址："[Song, Ya; Wang, Yanhui; Li, Chuanfei; Liao, Shengtao; Yu, Keqi; Mei, Zhechuan; Lv, Lin] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Song, Qian] Chongqing Med Univ, Coll Clin Med 2, 1 Yixue Rd, Chongqing 400016, Peoples R China; [Tan, Fangyan] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Lv, L (通讯作者)，Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：LIFE SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001336227100001

JCR分区：Q1

影响因子：6.1

年份：2024

卷号：351

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Ulcerative colitis; Seliciclib; Ferroptosis; Intestinal inflammation; DUOX2

摘要："Background: Ulcerative colitis (UC) is a chronic, recurrent, non-specific inflammatory disease, and the pathogenesis of the disease remains unclear. Ferroptosis is a form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which are simultaneously closely related to reactive oxygen species (ROS). Although seliciclib is highly effective against immune inflammation, its mechanism on colitis is unclear. This study demonstrated that seliciclib administration partially inhibited ferroptosis, alleviating symptoms and inflammation in experimental colitis. Methods: The mouse UC model was induced by 3.0 % dextran sodium sulfate (DSS) for 7 days and treated with seliciclib (10 mg/kg) for 5 days. In the in vitro model, LPS (100 mu g/mL) was used for induction and seliciclib (10 mu M) was applied for 2 h. Meanwhile, appropriate histopathology, inflammatory response, oxidative stress, and ferroptosis regulators were measured. Results: This study primarily investigated the role of seliciclib in regulating ferroptosis in UC. Bioinformatics analysis indicated that Dual oxidase 2 (DUOX2) may serve a role involved in the ferroptosis of UC. The experimental findings demonstrated that seliciclib alleviates symptoms and inflammation in DSS-induced UC mice and partially mitigates the occurrence of ferroptosis both in vivo and in vitro, possibly through the modulation of DUOX2. Conclusions: Ferroptosis is strongly associated with the development of colitis, and seliciclib plays an essential role in ferroptosis and inflammation in UC. The suppression of ferroptosis in the intestinal epithelium could be a therapeutic approach for UC."

基金机构："National Natural Science Foundation of China [82103206, 82173360]; General Project of Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0018]; Special Support for Chongqing Postdoctoral Research Project [2021XM3027]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University [kryc-yq-2224, 13-003-023]; Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2020GDRC014]; Senior Medical Talents Program of Chongqing for Young and Middle-aged [11-020]"

基金资助正文："This work was funded by the National Natural Science Foundation of China (Grant Numbers: 82103206, 82173360) , General Project of Natural Science Foundation of Chongqing (Grant Number: cstc2021jcyj-msxmX0018) , Special Support for Chongqing Postdoctoral Research Project (Grant Number: 2021XM3027) , Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (Grant Number: kryc-yq-2224, 13-003-023) , Senior Medical Talents Program of Chongqing for Young and Middle-aged (Grant Number: 11-020) , Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (Grant Number: 2020GDRC014) . No external <STRONG>Funding </STRONG>was received in this study."