1. Prevotella copripromotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway
- Author
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Hao, Qing-Yun, Yan, Jing, Wei, Jin-Tao, Zeng, Yu-Hong, Feng, Li-Yun, Que, Dong-Dong, Li, Shi-Chao, Guo, Jing-Bin, Fan, Ying, Ding, Yun-Fa, Zhang, Xiu-Li, Yang, Ping-Zhen, Gao, Jing-Wei, and Li, Ze-Hua more...
- Abstract
ABSTRACTEmerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri(P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copriand aortic calcification scores. Moreover, oral administration of live P. copriaggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitroand ex vivoexperiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copriin CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copriand its-derived LPS as potential therapeutic targets for VC in CKD. more...
- Published
- 2024
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