Lysosome-related Proteins May Have Changes in the Urinary Exosomes of Patients with Acute Gout Attack

Overview

Journal Eur J Med Res

Publisher Biomed Central

Date 2025 Jan 22

PMID 39838438

Authors

Jitu Wang

Na Liu

Mei Hu

Man Zhang

Affiliations

Soon will be listed here.

Abstract

Background: The autophagy-lysosome is intricately linked to the development of gout. At present, the diagnosis and monitoring of gout are mainly invasive tests, which cannot predict the occurrence of gout in the acute phase, and bring new pain to patients. This study focuses on the changes of lysosome-related proteins in urinary exosomes of patients with acute gout attack to explore the potential noninvasive biomarkers clinical application value.

Methods: Urine samples were collected from the subject and exosomes were extracted. To explore the differentially expressed proteins in urinary exosomes among acute gout patients (AD group), intermittent gout patients (ID group) and normal controls (NC group) by DIA mass spectrometry. Urinary exosomal lysosome associated proteins were analyzed and receiver operating characteristic (ROC) curves of differentially expressed proteins were drawn to evaluate their clinical value in monitoring acute gout attack.

Results: A total of 1896 proteins were detected between AD group and ID group, of which 121 proteins were differentially expressed (FC > 1.5 and p < 0.05). There were three lysosomal-related proteins differentially expressed in urinary exosomes between AD group and ID group. Compared with the ID group, the expression of Cathepsin Z (CTSZ) and AP-1 complex subunit beta-1 (AP1B1) was increased, while the expression of Lysosome-associated membrane glycoprotein 2 (LAMP2) was decreased in AD group. The ROC analysis showed that CTSZ, AP1B1 and LAMP2 had a strong ability to predict acute gout attack, with AUC of 0.826, 0.847 and 0.882, respectively.

Conclusions: There are many specific protein changes in the urinary exosomes of patients with acute gout attack. The urinary exosomes of patients with acute gout attack may exhibit alterations in lysosome-related proteins, particularly CTSZ, AP1B1, and LAMP2, which may become potential biomarkers for monitoring acute gout attack.

References

Wang L, Cai J, Zhao X, Ma L, Zeng P, Zhou L . Palmitoylation prevents sustained inflammation by limiting NLRP3 inflammasome activation through chaperone-mediated autophagy. Mol Cell. 2022; 83(2):281-297.e10. DOI: 10.1016/j.molcel.2022.12.002. View

Chen P, Wang Y, Tang H, Liu Z, Wang J, Wang T . Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases. Cell Immunol. 2024; 405-406:104888. DOI: 10.1016/j.cellimm.2024.104888. View

Alsaif H, Al-Owain M, Barrios-Llerena M, Gosadi G, Binamer Y, Devadason D . Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome. Am J Hum Genet. 2019; 105(5):1016-1022. PMC: 6848991. DOI: 10.1016/j.ajhg.2019.09.020. View

Cao Z, Wang Y, Long Z, He G . Interaction between autophagy and the NLRP3 inflammasome. Acta Biochim Biophys Sin (Shanghai). 2019; 51(11):1087-1095. DOI: 10.1093/abbs/gmz098. View

Thanassoulis G, Brophy J, Richard H, Pilote L . Gout, allopurinol use, and heart failure outcomes. Arch Intern Med. 2010; 170(15):1358-64. DOI: 10.1001/archinternmed.2010.198. View

Butler F, Alghubayshi A, Roman Y . The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis. J Pers Med. 2021; 11(3). PMC: 8005056. DOI: 10.3390/jpm11030231. View

Neogi T, Jansen T, Dalbeth N, Fransen J, Schumacher H, Berendsen D . 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 2015; 67(10):2557-68. PMC: 4566153. DOI: 10.1002/art.39254. View

Ravanan P, Srikumar I, Talwar P . Autophagy: The spotlight for cellular stress responses. Life Sci. 2017; 188:53-67. DOI: 10.1016/j.lfs.2017.08.029. View

Jin M, Yang F, Yang I, Yin Y, Luo J, Wang H . Uric acid, hyperuricemia and vascular diseases. Front Biosci (Landmark Ed). 2011; 17(2):656-69. PMC: 3247913. DOI: 10.2741/3950. View

10.

Zhou J, Chong S, Lim A, Singh B, Sinha R, Salmon A . Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging (Albany NY). 2017; 9(2):583-599. PMC: 5361683. DOI: 10.18632/aging.101181. View

11.

Chen S, Chen C, Shen M . Severity of gouty arthritis is associated with Q-wave myocardial infarction: a large-scale, cross-sectional study. Clin Rheumatol. 2006; 26(3):308-13. DOI: 10.1007/s10067-006-0292-4. View

12.

Wang J, Yang Q, Zhang Q, Yin C, Zhou L, Zhou J . Invariant Natural Killer T Cells Ameliorate Monosodium Urate Crystal-Induced Gouty Inflammation in Mice. Front Immunol. 2018; 8:1710. PMC: 5733058. DOI: 10.3389/fimmu.2017.01710. View

13.

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

14.

Dehlin M, Jacobsson L, Roddy E . Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020; 16(7):380-390. DOI: 10.1038/s41584-020-0441-1. View

15.

Zhang Q, Han M, Wang W, Song Y, Chen G, Wang Z . Downregulation of cathepsin L suppresses cancer invasion and migration by inhibiting transforming growth factor‑β‑mediated epithelial‑mesenchymal transition. Oncol Rep. 2015; 33(4):1851-9. DOI: 10.3892/or.2015.3754. View

16.

Campden R, Warren A, Greene C, Chiriboga J, Arnold C, Aggarwal D . Extracellular cathepsin Z signals through the α integrin and augments NLRP3 inflammasome activation. J Biol Chem. 2021; 298(1):101459. PMC: 8753182. DOI: 10.1016/j.jbc.2021.101459. View

17.

Song J, Jin C, Shan Z, Teng W, Li J . Prevalence and Risk Factors of Hyperuricemia and Gout: A Cross-sectional Survey from 31 Provinces in Mainland China. J Transl Int Med. 2022; 10(2):134-145. PMC: 9328039. DOI: 10.2478/jtim-2022-0031. View

18.

Bivik Eding C, Domert J, Waster P, Jerhammar F, Rosdahl I, Ollinger K . Melanoma growth and progression after ultraviolet a irradiation: impact of lysosomal exocytosis and cathepsin proteases. Acta Derm Venereol. 2015; 95(7):792-7. DOI: 10.2340/00015555-2064. View

19.

Allan E, Campden R, Ewanchuk B, Tailor P, Balce D, McKenna N . A role for cathepsin Z in neuroinflammation provides mechanistic support for an epigenetic risk factor in multiple sclerosis. J Neuroinflammation. 2017; 14(1):103. PMC: 5424360. DOI: 10.1186/s12974-017-0874-x. View

20.

Chen Y, Chen W, Yu C, Tsai C, Hsieh S . Gouty arthritis involves impairment of autophagic degradation via cathepsin D inactivation-mediated lysosomal dysfunction that promotes apoptosis in macrophages. Biochim Biophys Acta Mol Basis Dis. 2023; 1869(6):166703. DOI: 10.1016/j.bbadis.2023.166703. View