Dataset Information

Untargeted Metabolomics of the enthesis interstitial fluid of wild-type and Nlrp3-/- mice with sham operation and injury post 7 days

ABSTRACT: In order to investigate the effect of the NLRP3 inflammasome on the regeneration of enthesis, we established an enthesis injury and repair model in wild-type and NLRP3-/- mice. The interstitial fluid of enthesis was extracted, and untargeted metabolomics was conducted to discover differential metabolites between wild-type and NLRP3-/- mice.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12150 | MetaboLights | 2025-07-08

REPOSITORIES: MetaboLights

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Publications

The P2X7R/NLRP3 inflammasome axis suppresses enthesis regeneration through inflammatory and metabolic macrophage-stem cell cross-talk.

Gao Haihan H Wang Liren L Lyu Yangbao Y Jin Haocheng H Lin Zhiqi Z Kang Yuhao Y Li Ziyun Z Zhang Xueying X Jiang Yuhan Y Zhang Guoyang G Tao Zaijin Z Zhang Xiaofeng X Yang Bin B Bai Xingyu X Ma Xin X Liu Shen S Jiang Jia J

Science advances 20250425 17

The regeneration of the enthesis remains a formidable challenge in regenerative medicine. However, key regulators underlying unsatisfactory regeneration remain poorly understood. This study reveals that the purinergic receptor P2X7 (P2X7R)/Nod-like receptor family protein 3 (NLRP3) inflammasome axis suppresses enthesis regeneration by amplifying IL-1β-mediated inflammatory cross-talk and suppressing docosatrienoic acid (DTA) metabolic cross-talk. NLRP3 inflammasomes were activated in macrophages ...[more]

PMID: 40279432

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Project description:Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1beta (IL1B) maturation. The activation of NLRP3 inflammasome requires two-step signals. The first “priming” signal (Signal 1) enhances gene expression of inflammasome components. The second “activation” signal (Signal 2) promotes the assembly of inflammasome components. Deregulated activation of NLRP3 inflammasome contributes to the pathological processes of Alzheimer’s disease (AD) and multiple sclerosis (MS). However, at present, the precise mechanism regulating NLRP3 inflammasome activation and deactivation remains largely unknown. By genome-wide gene expression profiling, we studied the molecular network of NLRP3 inflammasome activation-responsive genes in a human monocyte cell line THP-1 sequentially given two-step signals. We identified the set of 83 NLRP3 inflammasome activation-responsive genes. Among them, we found the NR4A nuclear receptor family NR4A1, NR4A2, and NR4A3, the EGR family EGR1, EGR2, and EGR3, the IkappaB family NFKBIZ, NFKBID, and NFKBIA as a key group of the genes that possibly constitute a negative feedback loop for shutting down inflammation following NLRP3 inflammasome activation. By molecular network analysis, we identified a complex network of NLRP3 inflammasome activation-responsive genes involved in cellular development and death, and immune and inflammatory responses, where transcription factors AP-1, NR4A, and EGR serve as a hub. Thus, NLRP3 inflammasome activation-responsive genes constitute the molecular network composed of a set of negative feedback regulators for prompt resolution of inflammation. To load the Signal 1 (S1), THP-1 cells were incubated for 3 hours in the culture medium with or without inclusion of 0.2 microgram/ml lipopolysaccharide (LPS). To load the Signal 2 (S2), they were incubated further for 2 hours in the culture medium with inclusion of 10 microM nigericin sodium salt dissolved in ethanol or the equal v/v% concentration of ethanol (vehicle), followed by processing for microarray analysis on Human Gene 1.0 ST Array (Affymetrix).

			Action	DRS
	MWBD241049a_mix01.mzML	Mzml
	MWBD241049a_mix02.mzML	Mzml
	MWBD241049a_mix03.mzML	Mzml
	MWBD241049a_mix04.mzML	Mzml
	MWBD241049a_mix05.mzML	Mzml