{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:09Z","timestamp":1753892109050,"version":"3.41.2"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770542"],"award-info":[{"award-number":["81770542"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aimed to identify the biological functions of small intestine intestinal epithelial cell derived exosomes (IEC-Exos) and further distinguished the difference proteins in IEC-Exos between ileum and jejunum related to function of the digestive system and occurrence of several diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>IECs of Male C57BL\/6J mice were isolated. IEC-Exos were extracted from jejunum and ileum epithelial cell culture fluid by ultracentrifugation. In addition, isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS\/MS) were used to detect IEC-Exo proteins and conduct biological information analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that compared with jejunum IEC-Exos from ileum IEC-Exos, there were 393 up-regulated proteins and 346 down-regulated proteins. IECs-Exos, especially derived from jejunum, were rich in angiotensin-converting enzyme 2 (ACE2). The highly expressed proteins from ileum IEC-Exos were mostly enriched in genetic information processing pathways, which mainly mediate the processes of bile acid transport, protein synthesis and processing modification. In contrast, the highly expressed proteins from jejunum IEC-Exos were mainly enriched in metabolic pathways involved in sugar, fatty acid, amino acid, drug, and bone metabolism, etc. The differentially expressed proteins between ileum and jejunum IEC-Exos were not only related to the function of the digestive system but also closely related to the occurrence of infectious diseases, endocrine diseases and osteoarthritis, etc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IEC-Exos there were many differentially expressed proteins between ileum and jejunum, which played different roles in regulating intestinal biological functions. ACE2, the main host cell receptor of SARS-CoV-2, was highly expressed in IEC-Exos, which indicated that IEC-Exos may be a potential route of SARS-CoV-2 infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2022.773671","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T14:08:04Z","timestamp":1645625284000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhenyu","family":"Ding","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baokun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-021-00970-7","article-title":"Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease.","volume":"14","author":"Bickler","year":"2021","journal-title":"BMC Med. Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.drudis.2017.01.007","article-title":"Models for drug absorption from the small intestine: where are we and where are we going?","volume":"22","author":"Billat","year":"2017","journal-title":"Drug Discov. Today"},{"key":"B3","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/10409238.2020.1768207","article-title":"Retinol-binding protein 2 (RBP2): biology and pathobiology.","volume":"55","author":"Blaner","year":"2020","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115658","article-title":"Boronic acid-based arginase inhibitors in cancer immunotherapy.","volume":"28","author":"Borek","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"B5","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1172\/JCI103549","article-title":"Studies of intestinal digestion and absorption in the human.","volume":"36","author":"Borgstrom","year":"1957","journal-title":"J. Clin. Invest."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1111\/j.1530-0277.2012.01836.x","article-title":"Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human small intestine.","volume":"36","author":"Chiang","year":"2012","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.acthis.2011.09.002","article-title":"Immunohistochemical study of arginase 1 and 2 in various tissues of rats.","volume":"114","author":"Choi","year":"2012","journal-title":"Acta Histochem."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-1-14","article-title":"The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL\/6J mice.","volume":"1","author":"de Wit","year":"2008","journal-title":"BMC Med. Genomics"},{"key":"B9","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev-pharmtox-010611-134529","article-title":"Drug transporters in drug efficacy and toxicity.","volume":"52","author":"DeGorter","year":"2012","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4579","DOI":"10.3748\/wjg.v26.i31.4579","article-title":"COVID-19 pandemic: pathophysiology and manifestations from the gastrointestinal tract.","volume":"26","author":"Galanopoulos","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"555","DOI":"10.7705\/biomedica.v38i4.3897","article-title":"Polymorphisms in alcohol dehydrogenase (ADH1) and cytochrome p450 2E1 (CYP2E1) genes in patients with cirrhosis and\/or hepatocellular carcinoma.","volume":"38","author":"Gaviria-Calle","year":"2018","journal-title":"Biomedica"},{"key":"B12","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/s41574-019-0168-8","article-title":"Function and mechanisms of enteroendocrine cells and gut hormones in metabolism.","volume":"15","author":"Gribble","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nature24489","article-title":"A single-cell survey of the small intestinal epithelium.","volume":"551","author":"Haber","year":"2017","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2020.104422","article-title":"The role of extracellular vesicles in COVID-19 virus infection.","volume":"85","author":"Hassanpour","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20209610","article-title":"The protein expression profile of ACE2 in human tissues.","volume":"16","author":"Hikmet","year":"2020","journal-title":"Mol. Syst. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1007\/s00424-020-02411-3","article-title":"Structure, function and regulation of mammalian glucose transporters of the SLC2 family.","volume":"472","author":"Holman","year":"2020","journal-title":"Pflugers Arch."},{"key":"B17","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1253\/circj.cj-10-0045","article-title":"Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis.","volume":"74","author":"Imai","year":"2010","journal-title":"Circ. J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.3748\/wjg.v27.i19.2341","article-title":"Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19.","volume":"27","author":"Jin","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes.","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"B20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bpg.2016.02.007","article-title":"Physiology of intestinal absorption and secretion.","volume":"30","author":"Kiela","year":"2016","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-8-107","article-title":"The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes.","volume":"8","author":"Kohler","year":"2008","journal-title":"BMC Dev. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"7324","DOI":"10.1074\/jbc.M508382200","article-title":"Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids.","volume":"281","author":"Kono","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051641","article-title":"Transcriptional and metabolomic analysis of L-arginine\/nitric oxide pathway in inflammatory bowel disease and its association with local inflammatory and angiogenic response: preliminary findings.","volume":"21","author":"Krzystek-Korpacka","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1126\/science.abc1669","article-title":"SARS-CoV-2 productively infects human gut enterocytes.","volume":"369","author":"Lamers","year":"2020","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1016\/j.jprot.2010.06.006","article-title":"Exosomes: extracellular organelles important in intercellular communication.","volume":"73","author":"Mathivanan","year":"2010","journal-title":"J. Proteomics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1152\/physiolgenomics.00139.2017","article-title":"Sugar sensor genes in the murine gastrointestinal tract display a cephalocaudal axis of expression and a diurnal rhythm.","volume":"50","author":"O\u2019Brien","year":"2018","journal-title":"Physiol. Genomics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.biochi.2007.03.009","article-title":"Purification and characterization of human intestinal neutral ceramidase.","volume":"89","author":"Ohlsson","year":"2007","journal-title":"Biochimie"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121573","article-title":"Role of ceramidases in sphingolipid metabolism and human diseases.","volume":"8","author":"Parveen","year":"2019","journal-title":"Cells"},{"key":"B29","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/b978-0-12-816053-4.00021-3","article-title":"Exosomes.","volume":"88","author":"Pegtel","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"B30","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/0016-5085(89)90902-5","article-title":"Glutathione S-transferase, cytochrome P450, and uridine 5\u2019-diphosphate-glucuronosyltransferase in human small intestine and liver.","volume":"96","author":"Peters","year":"1989","journal-title":"Gastroenterology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and immune homeostasis.","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1159\/000511402","article-title":"COVID-19 and extracellular vesicles: an intriguing interplay.","volume":"45","author":"Pocsfalvi","year":"2020","journal-title":"Kidney Blood Press. Res."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106032","article-title":"Retinoblastoma binding protein 2 (RBP2) promotes HIF-1alpha-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway.","volume":"9","author":"Qi","year":"2014","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1080\/09168451.2016.1259552","article-title":"Molecular and cellular studies on the absorption, function, and safety of food components in intestinal epithelial cells.","volume":"81","author":"Satsu","year":"2017","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1124\/pr.118.015735","article-title":"Solute carrier transporters as potential targets for the treatment of metabolic disease.","volume":"72","author":"Schumann","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1136\/gut.15.6.444","article-title":"Functional differentiation of human jejunum and ileum: a comparison of the handling of glucose, peptides, and amino acids.","volume":"15","author":"Silk","year":"1974","journal-title":"Gut"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1124\/dmd.107.020321","article-title":"PDZK1 regulates two intestinal solute carriers (Slc15a1 and Slc22a5) in mice.","volume":"36","author":"Sugiura","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"B38","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1158\/2326-6066.CIR-20-0389","article-title":"Retinoic acid synthesis deficiency fosters the generation of polymorphonuclear myeloid-derived suppressor cells in colorectal cancer.","volume":"9","author":"Sun","year":"2021","journal-title":"Cancer Immunol. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1042\/bj2530759","article-title":"Isoenzymes of glutathione transferase in rat small intestine.","volume":"253","author":"Tahir","year":"1988","journal-title":"Biochem. J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-15831-7","article-title":"Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis.","volume":"11","author":"Tajik","year":"2020","journal-title":"Nat. Commun."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237044","article-title":"Exosome-mediated human norovirus infection.","volume":"15","author":"Todd","year":"2020","journal-title":"PLoS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"G251","DOI":"10.1152\/ajpgi.00102.2002","article-title":"The epithelial cell cytoskeleton and intracellular trafficking. II. Intestinal epithelial cell exosomes: perspectives on their structure and function.","volume":"283","author":"van Niel","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176413","article-title":"Alcohol addiction, gut microbiota, and alcoholism treatment: a review.","volume":"21","author":"Wang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191130","article-title":"Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine.","volume":"217","author":"Wang","year":"2020","journal-title":"J. Exp. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.molcel.2009.03.006","article-title":"How common are extraribosomal functions of ribosomal proteins?","volume":"34","author":"Warner","year":"2009","journal-title":"Mol. Cell."},{"key":"B46","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis.","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat. Methods"},{"key":"B47","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s12033-019-00163-9","article-title":"A high efficient method to isolate exosomes from small intestinal epithelium.","volume":"61","author":"Xia","year":"2019","journal-title":"Mol. Biotechnol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.clinre.2017.02.001","article-title":"An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: the apical sodium-dependent bile acid transporter (SLC10A2\/ASBT).","volume":"41","author":"Xiao","year":"2017","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jprot.2008.11.011","article-title":"Proteomic analysis of extracellular matrix and vesicles.","volume":"72","author":"Xiao","year":"2009","journal-title":"J. Proteomics"},{"key":"B50","first-page":"1029","article-title":"Expression profiling of fecal colonocytes for RNA-based screening of colorectal cancer.","volume":"31","author":"Yajima","year":"2007","journal-title":"Int. J. Oncol."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110835","article-title":"ASBT(SLC10A2): a promising target for treatment of diseases and drug discovery.","volume":"132","author":"Yang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.3892\/mmr.2019.9849","article-title":"Identification of key genes and pathways involved in microsatellite instability in colorectal cancer.","volume":"19","author":"Yu","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01464","article-title":"Exosome-induced regulation in inflammatory bowel disease.","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Immunol."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-019-1714-5","article-title":"High expression of FABP4 and FABP6 in patients with colorectal cancer.","volume":"17","author":"Zhang","year":"2019","journal-title":"World J. Surg. Oncol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1038\/s41591-020-0912-6","article-title":"Infection of bat and human intestinal organoids by SARS-CoV-2.","volume":"26","author":"Zhou","year":"2020","journal-title":"Nat. Med."},{"key":"B56","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/jmcb\/mjv014","article-title":"Ribosomal proteins: functions beyond the ribosome.","volume":"7","author":"Zhou","year":"2015","journal-title":"J. Mol. Cell Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1016.e9","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues.","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1210\/endo.139.7.6097","article-title":"Intestinal adaptation after extensive small bowel resection: differential changes in growth and insulin-like growth factor system messenger ribonucleic acids in jejunum and ileum.","volume":"139","author":"Ziegler","year":"1998","journal-title":"Endocrinology"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.773671\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T14:08:15Z","timestamp":1645625295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.773671\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":58,"alternative-id":["10.3389\/fphys.2022.773671"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.773671","relation":{},"ISSN":["1664-042X"],"issn-type":[{"type":"electronic","value":"1664-042X"}],"subject":[],"published":{"date-parts":[[2022,2,23]]},"article-number":"773671"}}