Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies.
Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies.
复制标题
磷脂酶A2对痛风性关节炎中自噬的调控：蛋白质组学与代谢组学研究
DOI：
10.1186/s12967-023-04114-6
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发表时间：
2023-04-17
影响因子：
7.4
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Fu, Weili;Ge, Minghao;Li, Jian
急性痛风性关节炎是炎症性关节炎。痛风性关节炎（GA）涉及多个病理过程。已证明，由硫酸盐（MSU）晶体沉积的关节在损伤过程中起着关键作用。由于MSU刺激对关节的影响不同，滑液的确切变化尚不清楚。我们想探讨痛风性关节炎关节中蛋白质和代谢物的变化。调节关节中的各种功能物质可以减少炎症和疼痛症状。从临床、手术病例中选择痛风性膝关节炎患者10例，正常对照组10例。通过共表达网络分析评估代谢组的生物学功能。基于代谢组学和蛋白质组学数据构建了一个分子网络来研究关键分子。然后通过蛋白质印迹验证相关通路中的基本分子变化。蛋白质组学分析显示，痛风性关节炎患者滑液中组织蛋白酶B、组织蛋白酶D、组织蛋白酶G和组织蛋白酶S的表达显著增加。富集分析显示溶酶体和临床炎症细胞形状变化之间呈正相关。非靶向代谢组学分析显示，痛风性关节炎患者的脂质和类脂质积聚，抑制自噬通量，并调节炎症和免疫。确定了磷脂酶A2等脂质物质的积累导致自噬-溶酶体复合物的不平衡状态，并鉴定了硬脂酰肉碱、十四酰肉碱、棕榈酰肉碱的差异表达代谢物（|log 2倍数变化|> 1.5，调整后的P值< 0.05，变量预测重要性（VIP）> 1.5）。发现自噬-溶酶体途径与痛风性膝关节炎相关。与正常对照相比，痛风性膝关节炎患者的多组学网络的基本分子改变涉及急性炎症反应、外泌体、免疫反应、溶酶体、亚油酸代谢和合成。蛋白质组学和非靶向代谢组学的综合分析揭示了痛风性关节炎中蛋白质和特征代谢物的改变，其主要涉及脂质和脂质样分子、磷脂酶A2和自噬溶酶体。本研究描述了痛风性膝关节炎的病理特征、发病途径、潜在的预测因素和治疗目标。在线版本包含补充材料，可通过10.1186/s12967-023-04114-6获得。
Acute gouty arthritis is inflammatory joint arthritis. Gouty arthritis (GA) involves multiple pathological processes. Deposition of joints by monosodium urate (MSU) crystals has been shown to play a critical role in the injury process. Due to the different effects of MSU stimulation on the joints, the exact changes in the synovial fluid are unknown. We want to explore the changes in proteins and metabolites in the joints of gouty arthritis. Regulating various functional substances in the joint can reduce inflammation and pain symptoms. 10 patients with gouty knee arthritis and 10 normal controls were selected from clinical, surgical cases. The biological function of the metabolome was assessed by co-expression network analysis. A molecular network based on metabolomic and proteomic data was constructed to study critical molecules. The fundamental molecular changes in the relevant pathways were then verified by western blot. Proteomic analysis showed that the expressions of proteases Cathepsin B, Cathepsin D, Cathepsin G, and Cathepsin S in synovial fluid patients with gouty arthritis were significantly increased. Enrichment analysis showed a positive correlation between lysosomal and clinical inflammatory cell shape changes. Untargeted metabolomic analysis revealed that lipids and lipoids accumulate, inhibit autophagic flux, and modulate inflammation and immunity in gouty arthritis patients. It was determined that the accumulation of lipid substances such as phospholipase A2 led to the imbalanced state of the autophagy-lysosome complex, and the differentially expressed metabolites of Stearoylcarnitine, Tetradecanoylcarnitine, Palmitoylcarnitine were identified (|log2 fold change|> 1.5, adjusted P value < 0.05 and variable importance in prediction (VIP) > 1.5). The autophagy-lysosomal pathway was found to be associated with gouty knee arthritis. Essential molecular alterations of multi-omics networks in gouty knee arthritis patients compared with normal controls involve acute inflammatory response, exosomes, immune responses, lysosomes, linoleic acid metabolism, and synthesis. Comprehensive analysis of proteomic and untargeted metabolomics revealed protein and characteristic metabolite alterations in gouty arthritis, it mainly involves lipids and lipid like molecules, phospholipase A2 and autophagic lysosomes. This study describes the pathological characteristics, pathways, potential predictors and treatment goals of gouty knee arthritis. The online version contains supplementary material available at 10.1186/s12967-023-04114-6.
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影响因子：
2.8
作者：
Hou, Jiehong;Gao, Wei
通讯作者：
Gao, Wei
DOI：
10.1007/978-981-16-2830-6_1
发表时间：
2021-01-01
期刊：
AUTOPHAGY: BIOLOGY AND DISEASES: TECHNOLOGY AND METHODOLOGY
影响因子：
--
作者：
Nie, Tiejian;Zhu, Lin;Yang, Qian
通讯作者：
Yang, Qian
影响因子：
7.8
作者：
ASHFORD, T P;PORTER, K R
通讯作者：
PORTER, K R
影响因子：
4.6
作者：
Pearson MJ;Herndler-Brandstetter D;Tariq MA;Nicholson TA;Philp AM;Smith HL;Davis ET;Jones SW;Lord JM
通讯作者：
Lord JM
影响因子：
6.7
作者：
Fattori, Victor;Staurengo-Ferrari, Larissa;Verri Jr, Waldiceu A.
通讯作者：
Verri Jr, Waldiceu A.