Exosomal miR-141-3p from PDLSCs Alleviates High Glucose-Induced Senescence of PDLSCs by Activating the KEAP1-NRF2 Signaling Pathway

作者全名："Liu, Min; Chen, Rui; Xu, Yunxuan; Zheng, Jiawen; Wang, Min; Wang, Ping"

作者地址："[Liu, Min; Xu, Yunxuan; Zheng, Jiawen; Wang, Min; Wang, Ping] Chongqing Med Univ, Affiliated Hosp 1, Dept Stomatol, Chongqing 400016, Peoples R China; [Chen, Rui] Chongqing Med Univ, Affiliated Hosp 1, Dept Oral & Maxillofacial Surg, Chongqing 400016, Peoples R China"

通信作者："Wang, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Stomatol, Chongqing 400016, Peoples R China."

来源：STEM CELLS INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000999014300001

JCR分区：Q2

影响因子：3.8

年份：2023

卷号：2023

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Human periodontal ligament stem cells (PDLSCs) are the most promising stem cells for periodontal tissue engineering. Senescent PDLSCs have diminished abilities to proliferate and differentiate, affecting the efficiency of periodontal tissue repair and regeneration. Stem cell-derived exosomes are important participants in intercellular information exchange and can help ameliorate senescence. In this study, we investigated PDLSC senescence in a high glucose microenvironment as well as the ability of human periodontal ligament stem cell-derived exosomes (PDLSC-Exos) to alleviate cellular senescence and the underlying mechanisms. Herein, PDLSCs and PDLSC-Exos were isolated and extracted. Then, cellular senescence indicators were evaluated after high glucose (25 mM) treatment of cultured PDLSCs. PDLSC-Exos were cocultured with senescent PDLSCs to further explore the role of PDLSC-Exos in cellular senescence and determine the differences in cellular oxidative stress levels after PDLSC-Exo treatment. Next, we investigated whether PDLSC-Exos alleviated cellular senescence by restoring the balance of oxidative stress signals and explored the underlying molecular pathways. We discovered that PDLSCs underwent premature senescence due to high glucose culture, but they were rejuvenated by PDLSC-Exos. The rejuvenating effects of PDLSC-Exos were notably reversed by cotreatment with ML385, an inhibitor of nuclear factor erythroid 2-related factor 2 (NRF2), indicating that this recovery depended on NRF2 activation. Further analyses revealed that microRNA-141-3p (miR-141-3p) was expressed at relatively high levels in PDLSC-Exos and was instrumental in PDLSC-Exo-mediated restoration by downregulating Kelch-like ECH-associated protein 1 (KEAP1), which is a negative regulator of NRF2 expression. Our findings suggest that PDLSC-Exos alleviate high glucose-induced senescence of PDLSCs by transferring miR-141-3p to activate the KEAP1-NRF2 signaling pathway. Based on this research, PDLSC-Exos may behave similarly to their parental PDLSCs and have significant effects on cellular senescence by delivering their encapsulated bioactive chemicals to target cells."

基金机构：Chongqing Science and Technology Commission Basic Research and Frontier Exploration Project [cstc2018jcyjAX0829]

基金资助正文：AcknowledgmentsThis work was supported by the Chongqing Science and Technology Commission Basic Research and Frontier Exploration Project (cstc2018jcyjAX0829).