Knockdown of TRIM22 regulates the expression of NF-κB/NLRP3 and alleviates inflammation and renal injury in mice with lupus nephritis
Main Article Content
Keywords
TRIM22, lupus nephritis (LN), inflammation, renal injury, NF-κB/NLRP3 axis
Abstract
Lupus nephritis (LN) is a common and clinically challenging complication of the systemic lupus erythematosus (SLE), but effective treatments remain imperative. Tripartite Motif Containing 22 (TRIM22) is a protein involved in various cellular processes, such as cell growth and inflammatory responses. However, the role and mechanism of TRIM22 in LN are still unclear. The aim of this study was to reveal the role of TRIM22 in LN and uncover the potential mechanisms. We discovered that TRIM22 is notably upregulated in renal tissues from patients with LN. Functionally, the knockdown of TRIM22 in lupus-prone MRL/lpr mice results in significant alleviation of LN symptoms, characterized by reduced proteinuria and improved renal function, as indicated by the lower serum levels of blood urea nitrogen and creatinine. Additionally, the intervention markedly decreases the deposition of immune complexes in the kidneys, further supporting the therapeutic potential of targeting TRIM22. Mechanically, the depletion of TRIM22 inhibits the NF-κB/NLRP3 pathway in mice with LN, but collectively, the knockdown of TRIM22 alleviates inflammation and renal injury in mice with LN via the NF-κB/NLRP3 axis.
References
2 Lamas A, Faria R, Marinho A, Vasconcelos C. The mosaic of systemic lupus erythematosus: From autoimmunity to autoinflammation and immunodeficiency and back. Autoimmun Rev. 2024;23(12):103675. 10.1016/j.autrev.2024.103675
3 Moysidou E, Christodoulou M, Lioulios G, Stai S, Karamitsos T, Dimitroulas T, et al. Lymphocytes change their phenotype and function in systemic lupus erythematosus and lupus nephritis. Int J Mol Sci. 2024;25(20):10905. 10.3390/ijms252010905
4 Fukumi F, Takashi Y. Animal models of spontaneous and drug-induced cutaneous lupus erythematosus. Autoimmun Rev. 2005;4:(6):345–50. 10.1016/j.autrev.2005.01.006
5 Inoue A, Watanabe M, Kondo T, Hirano S, Hatakeyama S. TRIM22 negatively regulates MHC-II expression. Biochim Biophys Acta Mol Cell Res. 2022;1869(10):119318. 10.1016/j.bbamcr.2022.119318
6 Boswell MT, Yindom LM, Hameiri-Bowen D, McHugh G, Dauya E, Bandason T, et al. TRIM22 genotype is not associated with markers of disease progression in children with HIV-1 infection. AIDS. 2021;35(15):2445–50. 10.1097/QAD.0000000000003053
7 Ren Y, Dong H, Jin R, Jiang J, Zhang X. TRIM22 actives PI3K/Akt/mTOR pathway to promote psoriasis through enhancing cell proliferation and inflammation and inhibiting autophagy. Cutan Ocul Toxicol. 2022;41(4):304–9. 10.1080/15569527.2022.2127750
8 Kang C, Lu Z, Zhu G, Chen Y, Wu Y. Knockdown of TRIM22 relieves oxygen-glucose deprivation/reoxygenation-induced apoptosis and inflammation through inhibition of NF-kappaB/NLRP3 axis. Cell Mol Neurobiol. 2021;41(2):341–51. 10.1007/s10571-020-00855-w
9 Wei Y, Huang X, Ma Y, Dai L. FOXC1-mediated TRIM22 regulates the excessive proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis via NF-kappaB signaling pathway. Mol Med Rep. 2022;26(4):304. 10.3892/mmr.2022.12820
10 Ye B, Lu Z. Role of TRIM22 in ulcerative colitis and its underlying mechanisms. Mol Med Rep. 2022;26(2):249. 10.3892/mmr.2022.12765
11 Tian J, Huang T, Chen J, Wang J, Chang S, Xu H, et al. SIRT1 slows the progression of lupus nephritis by regulating the NLRP3 inflammasome through ROS/TRPM2/Ca(2+) channel. Clin Exp Med. 2023;23(7):3465–78. 10.1007/s10238-023-01093-2
12 Ma Q, Xu M, Jing X, Qiu J, Huang S, Yan H, et al. Honokiol suppresses the aberrant interactions between renal resident macrophages and tubular epithelial cells in lupus nephritis through the NLRP3/IL-33/ST2 axis. Cell Death Dis. 2023;14(3):174. 10.1038/s41419-023-05680-9
13 Yang SR, Hua KF, Yang CY, Chen A, Weng JC, Tsai YL, et al. Cf-02, a novel benzamide-linked small molecule, blunts NF-kappaB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice. FASEB J. 2021;35(8):e21785. 10.1096/fj.202100047R
14 Chen C, Wu M, Zuo E, Wu X, Wu L, Liu H, et al. Diagnosis of systemic lupus erythematosus using cross-modal specific transfer fusion technology based on infrared spectra and metabolomics. Anal Chim Acta. 2024;1330:343302. 10.1016/j.aca.2024.343302
15 Huyin Yang DL, Yanping Wang. Physalin A exerts neuroprotective effects: Inhibition of OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells. Signa Vitae. 2023;19(6):168–74.
16 Ma KS, Lo JE, Kyttaris VC, Tsokos GC, Costenbader KH. Efficacy and safety of sodium-glucose co-transporter 2 inhibitors for the primary prevention of cardiovascular, renal events and safety outcomes in patients with systemic lupus erythematosus and comorbid type 2 diabetes: A population-based target trial emulation. Arthritis Rheumatol. 2024. 10.1002/art.43037
17 Feng Q, Yang Y, Qiao Y, Zheng Y, Yu X, Liu F, et al. Quercetin ameliorates diabetic kidney injury by inhibiting ferroptosis via activating Nrf2/HO-1 signaling pathway. Am J Chin Med. 2023;51(4):997–1018. 10.1142/S0192415X23500465
18 Wiegley N, Arora S, Norouzi S, Rovin B. A comprehensive and practical approach to the management of lupus nephritis in the current era. Adv Kidney Dis Health. 2024;31(3):234–45. 10.1053/j.akdh.2023.11.003
19 Himbert M, Jourde-Chiche N, Chapart L, Charles N, Baumstarck K, Daugas E. Anti-dsDNA IgE: A potential non-invasive test for prediction of lupus nephritis relapse. RMD Open. 2024;10(2):e004255. 10.1136/rmdopen-2024-004255
20 Wu D, Ai L, Sun Y, Yang B, Chen S, Wang Q, et al. Role of NLRP3 inflammasome in lupus nephritis and therapeutic targeting by phytochemicals. Front Pharmacol. 2021;12:621300. 10.3389/fphar.2021.621300
21 Oliveira CB, Lima CAD, Vajgel G, Sandrin-Garcia P. The role of NLRP3 inflammasome in lupus nephritis. Int J Mol Sci. 2021;22(22):12476. 10.3390/ijms222212476
22 Ji J, Ding K, Luo T, Zhang X, Chen A, Zhang D, et al. TRIM22 activates NF-κB signaling in glioblastoma by accelerating the degradation of IκBα. Cell Death Differ. 2021;28(1):367–81. 10.1038/s41418-020-00606-w
