sEV-Enriched Serum Preparations From Healthy Individuals Protect Against Acute Pancreatitis-Induced Intestinal Barrier Dysfunction Through miR-579-3p/ANXA3-Mediated Inhibition of NLRP3 Inflammasome Pyroptosis
By: Huiyuan Gu, Chenyue Tang, Yuqi Shi, Jiaqing Shen and Chunfang Xu
References
- Bei Y, Chen T, Banciu DD et al. (2017) Circulating exosomes in cardiovascular diseases. Adv Exp Med Biol 998:255–269.
https://doi.org/10.1007/978-981-10-4397-0_17 - Chavez L, Meguro J, Chen S et al. (2021) Circulating extracellular vesicles activate the pyroptosis pathway in the brain following ventilation-induced lung injury. J Neuroinflammation 18:310.
https://doi.org/10.1186/s12974-021-02364-z - Chevillet JR, Kang Q, Ruf IK et al. (2014) Quantitative and stoichio-metric analysis of the microRNA content of exosomes. Proc Natl Acad Sci USA 111:14888–14893.
https://doi.org/10.1073/pnas.1408301111 - Chopyk DM, Grakoui A (2020) Contribution of the intestinal micro-biome and gut barrier to hepatic disorders. Gastroenterology 159:849–863.
https://doi.org/10.1053/j.gastro.2020.04.077 - Deng W, Abliz A, Xu S et al. (2016) Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin. Mol Med Rep 14:3525–3534.
https://doi.org/10.3892/mmr.2016.5678 - Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379.
https://doi.org/10.1146/annurev-biochem-060308-103103 - Garg PK, Singh VP (2019) Organ failure due to systemic injury in acute pancreatitis. Gastroenterology 156:2008–2023.
https://doi.org/10.1053/j.gastro.2018.12.041 - Ge P, Luo Y, Okoye CS et al. (2020) Intestinal barrier damage, systemic inflammatory response syndrome, and acute lung injury: A troublesome trio for acute pancreatitis. Biomed Pharmacother 132:110770.
https://doi.org/10.1016/j.biopha.2020.110770 - Huang LY, Song JX, Cai H et al. (2022) Healthy serum-derived exosomes improve neurological outcomes and protect blood-brain barrier by inhibiting endothelial cell apoptosis and reversing autophagy-mediated tight junction protein reduction in rat stroke model. Front Cell Neurosci 16:841544.
https://doi.org/10.3389/fncel.2022.841544 - Kimiz-Gebologlu I, Oncel SS (2022) Exosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake. J Control Release 347:533–543.
https://doi.org/10.1016/j.jconrel.2022.05.027 - Krylova SV, Feng D (2023) The machinery of exosomes: Biogenesis, release, and uptake. Int J Mol Sci 24:1337.
https://doi.org/10.3390/ijms24021337 - Kylänpää ML, Repo H, Puolakkainen PA (2010) Inflammation and immunosuppression in severe acute pancreatitis. World J Gastroenterol 16:2867–2872.
https://doi.org/10.3748/wjg.v16.i23.2867 - Li X, Liu YJ, Wang Y et al. (2023a) Epoxy triglyceride enhances intestinal permeability via caspase-1/NLRP3/GSDMD and cGAS-STING pathways in dextran sulfate sodium-induced colitis mice. J Agric Food Chem 71:4371–4381.
https://doi.org/10.1021/acs.jafc.2c08134 - Lin T, Peng M, Zhu Q et al. (2024) S1PR2 participates in intestinal injury in severe acute pancreatitis by regulating macrophage pyroptosis. Front Immunol 15:1405622.
https://doi.org/10.3389/fimmu.2024.1405622 - Liu L, Cai Y, Deng C (2023) Identification of ANXA3 as a biomarker associated with pyroptosis in ischemic stroke. Eur J Med Res 28:596.
https://doi.org/10.1186/s40001-023-01564-y - Li Q, Wang T, Wang X et al. (2023b) Inhibition of sepsis-induced acute kidney injury via the circITCH-miR-579-3p-ZEB2 axis. Environ Toxicol 38:1217–1225.
https://doi.org/10.1002/tox.23682 - Lu X, Shi C, Fan C (2025) Involvement of circ_0029407 in caerulein-evoked cytotoxicity in human pancreatic cells via the miR-579-3p/TLR4/NF-κB pathway. Mol Biotechnol 67:1978–1990.
https://doi.org/10.1007/s12033-024-01175-w - Mair-Jenkins J, Saavedra-Campos M, Baillie JK et al. (2015) The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis. J Infect Dis 211:80–90.
https://doi.org/10.1093/infdis/jiu396 - Mathieu M, Martin-Jaular L, Lavieu G et al. (2019) Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 21:9–17.
https://doi.org/10.1038/s41556-018-0250-9 - Mayer J, Rau B, Gansauge F et al. (2000) Inflammatory mediators in human acute pancreatitis: Clinical and pathophysiological implications. Gut 47:546–552.
https://doi.org/10.1136/gut.47.4.546 - Mederos MA, Reber HA, Girgis MD (2021) Acute pancreatitis: A review. JAMA 325:382–390.
https://doi.org/10.1001/jama.2020.20317 - Naseer N, Zhang J, Bauer R et al. (2022) Salmonella enterica serovar typhimurium induces NAIP/NLRC4- and NLRP3/ASC-independent, caspase-4-dependent inflammasome activation in human intestinal epithelial cells. Infect Immun 90:e0066321.
https://doi.org/10.1128/iai.00663-21 - Pegtel DM, Gould SJ (2019) Exosomes. Annu Rev Biochem 88:487–514.
https://doi.org/10.1146/annurev-biochem-013118-111902 - Rai A, Huynh K, Cross J et al. (2025) Multi-omics identify hallmark protein and lipid features of small extracellular vesicles circulating in human plasma. Nat Cell Biol 27:2167–2185.
https://doi.org/10.1038/s41556-025-01795-7 - Rao Z, Zhu Y, Yang P et al. (2022) Pyroptosis in inflammatory diseases and cancer. Theranostics 12:4310–4329.
https://doi.org/10.7150/thno.71086 - Scaldaferri F, Pizzoferrato M, Gerardi V et al. (2012) The gut barrier: New acquisitions and therapeutic approaches. J Clin Gastroenterol 46(Suppl.):S12–17.
https://doi.org/10.1097/MCG.0b013e31826ae849 - Shao Y, Jiang Y, Wang J et al. (2024) Inhibition of circulating exosomes release with GW4869 mitigates severe acute pancreatitis-stimulated intestinal barrier damage through suppressing NLRP3 inflammasome-mediated pyroptosis. Int Immunopharmacol 126:111301.
https://doi.org/10.1016/j.intimp.2023.111301 - Shao Y, Li Y, Jiang Y et al. (2023) Circulating exosomal miR-155-5p contributes to severe acute pancreatitis-associated intestinal barrier injury by targeting SOCS1 to activate NLRP3 inflamma-some-mediated pyroptosis. FASEB J 37:e23003.
https://doi.org/10.1096/fj.202300237R - Sork H, Conceicao M, Corso G et al. (2021) Profiling of extracellular small RNAs highlights a strong bias towards non-vesicular secretion. Cells 10:1543.
https://doi.org/10.3390/cells10061543 - Vasudevan SO, Behl B, Rathinam VA (2023) Pyroptosis-induced inflammation and tissue damage. Semin Immunol 69:101781.
https://doi.org/10.1016/j.smim.2023.101781 - Wang Y, Jia L, Wei M et al. (2023) Circulating exosomes mediate neurodegeneration following hepatic ischemia-reperfusion through inducing microglial pyroptosis in the developing hippocampus. Transplantation 107:2364–2376.
https://doi.org/10.1097/tp.0000000000004664 - Wei Z, Hang S, Wiredu Ocansey DK et al. (2023) Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis. J Nanobiotechnology 21:188.
https://doi.org/10.1186/s12951-023-01951-x - Wortzel I, Dror S, Kenific CM et al. (2019) Exosome-mediated metastasis: Communication from a distance. Dev Cell 49:347–360.
https://doi.org/10.1016/j.devcel.2019.04.011 - Xu X, Huang Z, Huang Z et al. (2024) Butyrate attenuates intestinal inflammation in Crohn's disease by suppressing pyroptosis of intestinal epithelial cells via the cGSA-STING-NLRP3 axis. Int Immunopharmacol 143(Pt 2):113305.
https://doi.org/10.1016/j.intimp.2024.113305 - Yang W, Ding N, Luo R et al. (2023) Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury. Bioact Mater 27:1–14.
https://doi.org/10.1016/j.bioactmat.2023.03.007 - Yang J, Zheng XG, Wu YL et al. (2022) Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4. Biomed Pharmacother 149:112810.
https://doi.org/10.1016/j.biopha.2022.112810 - Ye J, Dai H, Liu Y et al. (2020) Blockade of C3a/C3aR axis alleviates severe acute pancreatitis-induced intestinal barrier injury. Am J Transl Res 12:6290–6301.
- Zerem E (2014) Treatment of severe acute pancreatitis and its complications. World J Gastroenterol 20:13879–13892.
https://doi.org/10.3748/wjg.v20.i38.13879 - Zhang J, Li S, Li L et al. (2015) Exosome and exosomal microRNA: Trafficking, sorting, and function. Genomics Proteomics Bioinformatics 13:17–24.
https://doi.org/10.1016/j.gpb.2015.02.001 - Zhdanov VP (2022) Interplay of cellular mRNA, miRNA and viral miRNA during Infection of a cell. Int J Mol Sci 24:122.
https://doi.org/10.3390/ijms24010122 - Zhou W, Dong S, Chen Z et al. (2022) New challenges for microRNAs in acute pancreatitis: Progress and treatment. J Transl Med 20:192.
https://doi.org/10.1186/s12967-022-03338-2 - Zhou Q, Xiang H, Liu H et al. (2021) Emodin alleviates intestinal barrier dysfunction by inhibiting apoptosis and regulating the immune response in severe acute pancreatitis. Pancreas 50:1202–1211.
https://doi.org/10.1097/mpa.0000000000001894
DOI: https://doi.org/10.2478/aite-2026-0018 | Journal eISSN: 1661-4917
Language: English
Submitted on: Jan 16, 2026
Accepted on: Mar 10, 2026
Published on: Jun 25, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year
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© 2026 Huiyuan Gu, Chenyue Tang, Yuqi Shi, Jiaqing Shen, Chunfang Xu, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.