Intestinal metabolite UroB alleviates cerebral ischemia/reperfusion injury by promoting competition between TRIM65 and TXNIP for binding to NLRP3 inflammasome in response to neuroinflammation
作者全名："Luo, Jing; Luo, Yujia; Chen, Jialei; Gao, Yu; Tan, Junyi; Yang, Yongkang; Yang, Changhong; Jiang, Ning; Luo, Yong"
作者地址："[Luo, Jing; Luo, Yong] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [Luo, Jing; Gao, Yu; Jiang, Ning] Chongqing Med Univ, Dept Pathol, Chongqing, Peoples R China; [Luo, Jing; Gao, Yu; Jiang, Ning] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing, Peoples R China; [Luo, Jing; Gao, Yu; Jiang, Ning] Chongqing Med Univ, Dept Pathol, Affiliated Hosp 1, Chongqing, Peoples R China; [Luo, Yujia] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing, Peoples R China; [Chen, Jialei] Chongqing Med Univ, Coll Basic Med Sci, Mol Med & Canc Res Ctr, Chongqing, Peoples R China; [Chen, Jialei; Tan, Junyi] Chongqing Med Univ, Dept Pathol & Pathophysiol, Chongqing, Peoples R China; [Yang, Yongkang] Chengdu Univ, Dept Clin Med, Clin Med Coll, Chengdu, Peoples R China; [Yang, Changhong] Chongqing Med Univ, Dept Bioinformat, Chongqing, Peoples R China"
通信作者："Luo, Y (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China.; Jiang, N (通讯作者)，Chongqing Med Univ, Dept Pathol, Chongqing, Peoples R China."
来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001197213900001
JCR分区：Q1
影响因子：6.2
年份：2024
卷号：1870
期号：4
开始页：
结束页：
文献类型：Article
关键词：Cerebral ischemia/reperfusion; UroB; TXNIP; TRIM65; NLRP3 inflammasome; Neuroinflammation
摘要："Our previous research suggests that targeting NLRP3 inflammasomes holds promise for mitigating cerebral ischemia/reperfusion injury. The gut metabolite Urolithin B (UroB) has been shown to inhibit the neuroinflammation. However, the specific role of UroB in cerebral ischemia/reperfusion injury and its potential impact on NLRP3 inflammasome remain unclear. In this study, acute stroke was simulated using the MCAO model in male Sprague-Dawley rats. UroB was intraperitoneally administered after 1 h of reperfusion. The effects of UroB on brain tissue were evaluated, including infarct volume, brain edema, and neurobehavioral changes. Western blotting and immunofluorescence were performed to investigate the effect of UroB on inflammation-related proteins. Furthermore, TRIM65 knockdown and TXNIP overexpression experiments elucidated the role of UroB in NLRP3 inflammasome activation. The ( demonstrate the neuroprotective effect of UroB in acute stroke, reducing brain tissue damage and improving motor function. Mechanistically, UroB modulated neuroinflammation by influencing TXNIP and TRIM65 protein expression, as well as competitive binding to the NLRP3 inflammasome, attenuating cerebral ischemia/reperfusion injury. In conclusion, the potential of UroB as a protective agent against cerebral ischemia/reperfusion injury in acute stroke stands out as it regulates TRIM65 and TXNIP competitive binding to the NLRP3 inflammasome. These findings suggest that UroB is a promising drug candidate for the treatment of acute stroke."
基金机构：Natural Science Foundation of Chongqing; Science and technology research program of Chongqing Education Commission of China [KJQN202000401]
基金资助正文："<BOLD>Acknowledgements</BOLD> This study was supported by the Natural Science Foundation of Chongqing (No.cstc2020jcyj-bshX0069) , and Science and technology research program of Chongqing Education Commission of China (KJQN202000401) ."
