The NLRP3 molecule influences the therapeutic effects of mesenchymal stem cells through Glut1-mediated energy metabolic reprogramming

作者：Jingrou Chen, Shu‐Juan Xie, Dongbo Qiu, Maosheng Xie, Mengye Wu, Xiaoping Li, Xiaoran Zhang, Qili Wu, Yi Xiong, Changyou Wu, Jie Ren, Yanwen Peng · 发表于：Journal of Advanced Research · 年份：2023 · DOI：10.1016/j.jare.2023.12.006 · 被引用次数：24 · 研究领域：Inflammasome and immune disorders、Mesenchymal stem cell research、Immune cells in cancer

INTRODUCTION: Numerous studies demonstrated that NLRP3 has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) regulated the NLRP3 inflammasome, which has emerged as a novel therapeutic approach for treating IBD. OBJECTIVES: The exact role of NLRP3 in regulating MSCs' function is unclear. Our study aimed to explore how NLRP3 affects the therapeutic effects of MSCs in colitis. METHODS: We extracted MSCs from the bone marrow of C57BL/6 mice and Nlrp3 KO mice, and identified them using differentiation assays and flow cytometry. In vitro, Both WT MSCs and Nlrp3 KO MSCs were stimulated with inflammatory factor Lipopolysaccharide (LPS), and only WT MSCs were stimulated with varying concentrations of the NLRP3 inhibitor MCC950, then, quantified IL-10 levels in the supernatant. RNA-seq was performed to examine gene expression patterns and Seahorse was used to assess oxidative phosphorylation (OXPHOS) and glycolysis levels. Western blot was used to evaluate protein expression. In vivo, we treated DSS-induced colitis with either WT or Nlrp3 KO MSCs, monitoring weight, measuring colon length, and further evaluation. We also treated DSS-induced colitis with pretreated MSCs (BAY876, oe-Glut1, or oe-NLRP3), following the same experimental procedures as described above. RESULTS: Our results demonstrate that Nlrp3 deletion did not affect MSC phenotypes, but rather promoted osteogenic differentiation. However, the absence of Nlrp3 reduced IL-...