{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:27:16Z","timestamp":1794266836095,"version":"4.9.0"},"reference-count":92,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01 DK123078"],"award-info":[{"award-number":["R01 DK123078"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["6 U54OH011230-06-02"],"award-info":[{"award-number":["6 U54OH011230-06-02"]}]},{"name":"Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health of the U.S. Department of Health and Human Services","award":["R01 DK123078"],"award-info":[{"award-number":["R01 DK123078"]}]},{"name":"Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health of the U.S. Department of Health and Human Services","award":["6 U54OH011230-06-02"],"award-info":[{"award-number":["6 U54OH011230-06-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Extracellular vesicles (EVs) include exosomes, microvesicles, and apoptotic bodies. EVs are released by all cell types and are found in biological fluids including plasma and urine. Urinary extracellular vesicles (uEVs) are a mixed population of EVs that comprise small EVs that are filtered and excreted, EVs secreted by tubular epithelial cells, and EVs released from the bladder, urethra, and prostate. The packaged cargo within uEVs includes bioactive molecules such as metabolites, lipids, proteins, mRNAs, and miRNAs. These molecules are involved in intercellular communication, elicit changes in intracellular signaling pathways, and play a role in the pathogenesis of various diseases including diabetes-associated hypertension and diabetic nephropathy. uEVs represent a rich source of biomarkers, prognosis markers, and can be loaded with small-molecule drugs as a vehicle for delivery.<\/jats:p>","DOI":"10.3390\/biology12081138","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T09:57:02Z","timestamp":1692179822000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Extracellular Vesicles: Investigating the Pathophysiology of Diabetes-Associated Hypertension and Diabetic Nephropathy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4381-1172","authenticated-orcid":false,"given":"Abdel A.","family":"Alli","sequence":"first","affiliation":[{"name":"Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nrneph.2017.148","article-title":"Isolation and characterization of urinary extracellular vesicles: Implications for biomarker discovery","volume":"13","author":"Merchant","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22865","DOI":"10.3402\/jev.v3.22865","article-title":"Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34)","volume":"3","author":"Madison","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jella, K.K., Yu, L., Yue, Q., Friedman, D., Duke, B.J., and Alli, A.A. (2016). Exosomal GAPDH from Proximal Tubule Cells Regulate ENaC Activity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165763"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3109\/01913123.2014.981327","article-title":"Intercellular communication by extracellular vesicles with emphasis on the roles of cordocytes in the human brain. An ultrastructural study","volume":"39","author":"Pais","year":"2015","journal-title":"Ultrastruct. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/ar.24181","article-title":"Extracellular Vesicles and Cell-Cell Communication in the Cornea","volume":"303","author":"Zieske","year":"2020","journal-title":"Anat. Rec. (Hoboken)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11754","DOI":"10.7150\/thno.43163","article-title":"Cardiomyocyte-derived small extracellular vesicles can signal eNOS activation in cardiac microvascular endothelial cells to protect against Ischemia\/Reperfusion injury","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pekkucuksen, N.T., Liu, L.P., Aly, R., Shoemaker, L.R., and Alli, A.A. (2022). Extracellular vesicles from focal segmental glomerulosclerosis pediatric patients induce STAT3 activation and mesangial cell proliferation. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274598"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e12264","DOI":"10.1002\/jev2.12264","article-title":"Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway","volume":"11","author":"Wei","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12276","DOI":"10.1002\/jev2.12276","article-title":"Extracellular vesicles derived from the choroid plexus trigger the differentiation of neural stem cells","volume":"11","author":"Ditte","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ito, A., Kagawa, S., Sakamoto, S., Kuwada, K., Kajioka, H., Yoshimoto, M., Kikuchi, S., Kuroda, S., Yoshida, R., and Tazawa, H. (2021). Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-07816-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2200252119","DOI":"10.1073\/pnas.2200252119","article-title":"Extracellular vesicles secreted by human uterine stromal cells regulate decidualization, angiogenesis, and trophoblast differentiation","volume":"119","author":"Ma","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/s42003-023-04859-2","article-title":"High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications","volume":"6","author":"Alter","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Antich-Rossello, M., Munar-Bestard, M., Forteza-Genestra, M.A., Calvo, J., Gaya, A., Monjo, M., and Ramis, J.M. (2022). Evaluation of Platelet-Derived Extracellular Vesicles in Gingival Fibroblasts and Keratinocytes for Periodontal Applications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147668"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/10717544.2020.1869866","article-title":"Preservation of small extracellular vesicles for functional analysis and therapeutic applications: A comparative evaluation of storage conditions","volume":"28","author":"Wu","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lopez, J.P., Nouri, M.Z., Ebrahim, A., Chacko, K.M., Schramm, W.C., Gholam, M.F., Ozrazgat-Baslanti, T., Denslow, N.D., and Alli, A.A. (2022). Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315397"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Darwish, S., Liu, L.P., Robinson, T.O., Tarugu, S., Owings, A.H., Glover, S.C., and Alli, A.A. (2023). COVID-19 Plasma Extracellular Vesicles Increase the Density of Lipid Rafts in Human Small Airway Epithelial Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021654"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Muraoka, S., Jedrychowski, M.P., Yanamandra, K., Ikezu, S., Gygi, S.P., and Ikezu, T. (2020). Proteomic Profiling of Extracellular Vesicles Derived from Cerebrospinal Fluid of Alzheimer\u2019s Disease Patients: A Pilot Study. Cells, 9.","DOI":"10.3390\/cells9091959"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.18632\/oncotarget.13634","article-title":"Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer","volume":"8","author":"Sequeiros","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12300","DOI":"10.1002\/jev2.12300","article-title":"Identification of faecal extracellular vesicles as novel biomarkers for the non-invasive diagnosis and prognosis of colorectal cancer","volume":"12","author":"Zhang","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1039\/D1BM02005F","article-title":"Extracellular vesicles with high dual drug loading for safe and efficient combination chemo-phototherapy","volume":"10","author":"Kim","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1021\/acs.nanolett.0c04753","article-title":"A Biomimetic Drug Delivery System by Integrating Grapefruit Extracellular Vesicles and Doxorubicin-Loaded Heparin-Based Nanoparticles for Glioma Therapy","volume":"21","author":"Niu","year":"2021","journal-title":"Nano Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1157194","DOI":"10.3389\/fendo.2023.1157194","article-title":"Therapeutic potential of urine exosomes derived from rats with diabetic kidney disease","volume":"14","author":"Mishra","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00277-019-03866-w","article-title":"Evaluation of dsDNA from extracellular vesicles (EVs) in pediatric AML diagnostics","volume":"99","author":"Kontopoulou","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1080\/0886022X.2022.2118067","article-title":"Extracellular vesicles metabolic changes reveals plasma signature in stage-dependent diabetic kidney disease","volume":"44","author":"Pan","year":"2022","journal-title":"Ren. Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"215735","DOI":"10.1016\/j.canlet.2022.215735","article-title":"Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer","volume":"542","author":"Wang","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1021\/acs.nanolett.0c04476","article-title":"Magnetic Colloid Antibodies Accelerate Small Extracellular Vesicles Isolation for Point-of-Care Diagnostics","volume":"21","author":"Yang","year":"2021","journal-title":"Nano Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.ymthe.2021.01.020","article-title":"A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties","volume":"29","author":"Dooley","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1016\/j.ymthe.2022.06.003","article-title":"MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson\u2019s disease","volume":"30","author":"Esteves","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E4165","DOI":"10.1073\/pnas.1416745111","article-title":"Modeling putative therapeutic implications of exosome exchange between tumor and immune cells","volume":"111","author":"Lu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/sctm.19-0059","article-title":"Predicting Functional Responses of Progenitor Cell Exosome Potential with Computational Modeling","volume":"8","author":"Trac","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e979","DOI":"10.1002\/ctm2.979","article-title":"Cardiac troponin T in extracellular vesicles as a novel biomarker in human cardiovascular disease","volume":"12","author":"Lennon","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Paluschinski, M., Loosen, S., Kordes, C., Keitel, V., Kuebart, A., Brandenburger, T., Scholer, D., Wammers, M., Neumann, U.P., and Luedde, T. (2023). Extracellular Vesicles as Markers of Liver Function: Optimized Workflow for Biomarker Identification in Liver Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119631"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105416","DOI":"10.1016\/j.isci.2022.105416","article-title":"Urinary extracellular vesicles signature for diagnosis of kidney disease","volume":"25","author":"Takizawa","year":"2022","journal-title":"iScience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1242\/bio.015990","article-title":"Exosomes from high glucose-treated glomerular endothelial cells activate mesangial cells to promote renal fibrosis","volume":"5","author":"Wu","year":"2016","journal-title":"Biol. Open"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1681\/ASN.2012101031","article-title":"TGF-beta1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis","volume":"24","author":"Borges","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Jeon, J.S., Kim, E., Bae, Y.U., Yang, W.M., Lee, H., Kim, H., Noh, H., Han, D.C., Ryu, S., and Kwon, S.H. (2020). microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells. Cells, 9.","DOI":"10.3390\/cells9061409"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/prca.201400198","article-title":"Circadian exosomal expression of renal thiazide-sensitive NaCl cotransporter (NCC) and prostasin in healthy individuals","volume":"9","author":"Castagna","year":"2015","journal-title":"Proteomics Clin. Appl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1038\/s41440-021-00710-5","article-title":"Characterization of pendrin in urinary extracellular vesicles in a rat model of aldosterone excess and in human primary aldosteronism","volume":"44","author":"Tsurutani","year":"2021","journal-title":"Hypertens. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00424-017-2049-0","article-title":"Acute regulated expression of pendrin in human urinary exosomes","volume":"470","author":"Pathare","year":"2018","journal-title":"Pflugers Arch."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1074\/mcp.R600004-MCP200","article-title":"Discovery of urinary biomarkers","volume":"5","author":"Pisitkun","year":"2006","journal-title":"Mol. Cell. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1161\/HYPERTENSIONAHA.121.17263","article-title":"Activation of Rac1-Mineralocorticoid Receptor Pathway Contributes to Renal Injury in Salt-Loaded db\/db Mice","volume":"78","author":"Hirohama","year":"2021","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lugo, C.I., Liu, L.P., Bala, N., Morales, A.G., Gholam, M.F., Abchee, J.C., Elmoujahid, N., Elshikha, A.S., Avdiaj, R., and Searcy, L.A. (2022). Human Alpha-1 Antitrypsin Attenuates ENaC and MARCKS and Lowers Blood Pressure in Hypertensive Diabetic db\/db Mice. Biomolecules, 13.","DOI":"10.3390\/biom13010066"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Scindia, Y.M., Gholam, M.F., Waleed, A., Liu, L.P., Chacko, K.M., Desai, D., Lopez, J.P., Malik, Z., Schramm, W.C., and Morales, A.G. (2023). Metformin Alleviates Diabetes-Associated Hypertension by Attenuating the Renal Epithelial Sodium Channel. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020305"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1681\/ASN.2020081112","article-title":"Renal Inflammation Induces Salt Sensitivity in Male db\/db Mice through Dysregulation of ENaC","volume":"32","author":"Veiras","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.bbrc.2018.06.075","article-title":"Plasma exosomes regulate systemic blood pressure in rats","volume":"503","author":"Otani","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1161\/HYPERTENSIONAHA.119.13363","article-title":"Circulating Extracellular Vesicles in Normotension Restrain Vasodilation in Resistance Arteries","volume":"75","author":"Good","year":"2020","journal-title":"Hypertension"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1161\/HYPERTENSIONAHA.118.11766","article-title":"Loss of Renal Peritubular Capillaries in Hypertensive Patients Is Detectable by Urinary Endothelial Microparticle Levels","volume":"72","author":"Sun","year":"2018","journal-title":"Hypertension"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e12164","DOI":"10.1002\/jev2.12164","article-title":"Proteomic dissection of large extracellular vesicle surfaceome unravels interactive surface platform","volume":"10","author":"Rai","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7932765","DOI":"10.1155\/2016\/7932765","article-title":"miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy","volume":"2016","author":"Jia","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mohan, A., Singh, R.S., Kumari, M., Garg, D., Upadhyay, A., Ecelbarger, C.M., Tripathy, S., and Tiwari, S. (2016). Urinary Exosomal microRNA-451-5p Is a Potential Early Biomarker of Diabetic Nephropathy in Rats. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154055"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.diabet.2018.08.004","article-title":"MicroRNAs from urinary extracellular vesicles are non-invasive early biomarkers of diabetic nephropathy in type 2 diabetes patients with the \u2018Asian Indian phenotype\u2019","volume":"45","author":"Prabu","year":"2019","journal-title":"Diabetes Metab."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Delic, D., Eisele, C., Schmid, R., Baum, P., Wiech, F., Gerl, M., Zimdahl, H., Pullen, S.S., and Urquhart, R. (2016). Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150154"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Barutta, F., Tricarico, M., Corbelli, A., Annaratone, L., Pinach, S., Grimaldi, S., Bruno, G., Cimino, D., Taverna, D., and Deregibus, M.C. (2013). Urinary exosomal microRNAs in incipient diabetic nephropathy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073798"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kalani, A., Mohan, A., Godbole, M.M., Bhatia, E., Gupta, A., Sharma, R.K., and Tiwari, S. (2013). Wilm\u2019s tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060177"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.trsl.2015.05.007","article-title":"Kidney tissue proteomics reveals regucalcin downregulation in response to diabetic nephropathy with reflection in urinary exosomes","volume":"166","author":"Zubiri","year":"2015","journal-title":"Transl. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"289734","DOI":"10.1155\/2015\/289734","article-title":"Proteases and protease inhibitors of urinary extracellular vesicles in diabetic nephropathy","volume":"2015","author":"Musante","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Gholam, M.F., Liu, L.P., Searcy, L.A., Denslow, N.D., and Alli, A.A. (2023). Dapagliflozin Treatment Augments Bioactive Phosphatidylethanolamine Concentrations in Kidney Cortex Membrane Fractions of Hypertensive Diabetic db\/db Mice and Alters the Density of Lipid Rafts in Mouse Proximal Tubule Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021408"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E1280","DOI":"10.1210\/jc.2015-2270","article-title":"The Effect of Glucose on the Release and Bioactivity of Exosomes From First Trimester Trophoblast Cells","volume":"100","author":"Rice","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"F664","DOI":"10.1152\/ajprenal.00292.2020","article-title":"Decreased secretion and profibrotic activity of tubular exosomes in diabetic kidney disease","volume":"319","author":"Wen","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000020661","article-title":"Inhibiting albumin glycation ameliorates diabetic nephropathy in the db\/db mouse","volume":"8","author":"Cohen","year":"2000","journal-title":"Exp. Nephrol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1023\/B:REMD.0000032410.75638.da","article-title":"Pathogenesis of hypertension in diabetes","volume":"5","author":"Stas","year":"2004","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1161\/01.ATV.0000172688.26838.9f","article-title":"Type 2 diabetic mice have increased arteriolar tone and blood pressure: Enhanced release of COX-2-derived constrictor prostaglandins","volume":"25","author":"Bagi","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"H621","DOI":"10.1152\/ajpheart.00825.2011","article-title":"Altered clock gene expression and vascular smooth muscle diurnal contractile variations in type 2 diabetic db\/db mice","volume":"302","author":"Su","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1161\/01.ATV.0000252068.89775.ee","article-title":"Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor\/STAT3 signaling pathways involved in energy balance","volume":"27","author":"Bodary","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bellini, S., Saraceno, C., Benussi, L., Geviti, A., Longobardi, A., Nicsanu, R., Cimini, S., Ricci, M., Canafoglia, L., and Coppola, C. (2022). Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in GRN\/C9orf72 and Sporadic Frontotemporal Lobar Degeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810693"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/jcb.26219","article-title":"Hydrogen Peroxide Stimulates Exosomal Cathepsin B Regulation of the Receptor for Advanced Glycation End-Products (RAGE)","volume":"119","author":"Downs","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1074\/jbc.RA118.006142","article-title":"Modulation of calreticulin expression reveals a novel exosome-mediated mechanism of Z variant alpha(1)-antitrypsin disposal","volume":"294","author":"Khodayari","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.lfs.2018.08.024","article-title":"The role of cathepsin B in autophagy during obesity: A systematic review","volume":"209","author":"Araujo","year":"2018","journal-title":"Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1210\/jc.2005-1601","article-title":"Weight loss reduces adipose tissue cathepsin S and its circulating levels in morbidly obese women","volume":"91","author":"Taleb","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1530\/JOE-20-0408","article-title":"Circulating cathepsin S improves glycaemic control in mice","volume":"248","author":"Karimkhanloo","year":"2021","journal-title":"J. Endocrinol."},{"key":"ref_71","first-page":"832642","article-title":"Proteases in Plasma and Kidney of db\/db Mice as Markers of Diabetes-Induced Nephropathy","volume":"2011","author":"Winberg","year":"2011","journal-title":"ISRN Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.kint.2016.06.018","article-title":"Exogenous kallikrein protects against diabetic nephropathy","volume":"90","author":"Liu","year":"2016","journal-title":"Kidney Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41467-020-20500-w","article-title":"High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance","volume":"12","author":"Kumar","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e22177","DOI":"10.1096\/fj.202101323R","article-title":"Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3","volume":"36","author":"Abdelsaid","year":"2022","journal-title":"FASEB J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1046495","DOI":"10.3389\/fcvm.2023.1046495","article-title":"Contribution of adipocyte Na\/K-ATPase alpha1\/CD36 signaling induced exosome secretion in response to oxidized LDL","volume":"10","author":"Pillai","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"eabc9061","DOI":"10.1126\/sciadv.abc9061","article-title":"Circadian regulation of protein cargo in extracellular vesicles","volume":"8","author":"Yeung","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"F1098","DOI":"10.1152\/ajprenal.00568.2017","article-title":"Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101","volume":"317","author":"Koritzinsky","year":"2019","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H1634","DOI":"10.1152\/ajpheart.00257.2008","article-title":"Hypertension and disrupted blood pressure circadian rhythm in type 2 diabetic db\/db mice","volume":"295","author":"Su","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.biochi.2015.06.029","article-title":"Circadian phenotyping of obese and diabetic db\/db mice","volume":"124","author":"Grosbellet","year":"2016","journal-title":"Biochimie"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/0748730418803719","article-title":"A Novel Diabetic Mouse Model for Real-Time Monitoring of Clock Gene Oscillation and Blood Pressure Circadian Rhythm","volume":"34","author":"Hou","year":"2019","journal-title":"J. Biol. Rhythms"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1113\/expphysiol.2008.046474","article-title":"Cardiovascular and autonomic phenotype of db\/db diabetic mice","volume":"94","author":"Senador","year":"2009","journal-title":"Exp. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/nep.13451","article-title":"Glomerular mesangial cell and podocyte injuries in diabetic nephropathy","volume":"23","author":"Tung","year":"2018","journal-title":"Nephrology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"F280","DOI":"10.1152\/ajprenal.00375.2021","article-title":"Zebrafish (Danio rerio) larva as an in vivo vertebrate model to study renal function","volume":"322","author":"Bolten","year":"2022","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"12369","DOI":"10.1073\/pnas.0913667107","article-title":"Paradoxical glomerular filtration of carbon nanotubes","volume":"107","author":"Ruggiero","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.1096\/fj.201700417R","article-title":"Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells","volume":"31","author":"Dang","year":"2017","journal-title":"FASEB J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1681\/ASN.2008040406","article-title":"Large-scale proteomics and phosphoproteomics of urinary exosomes","volume":"20","author":"Gonzales","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e12304","DOI":"10.1002\/jev2.12304","article-title":"An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles","volume":"12","author":"Barreiro","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e12064","DOI":"10.1002\/jev2.12064","article-title":"Molecular and functional profiling of apical versus basolateral small extracellular vesicles derived from primary human proximal tubular epithelial cells under inflammatory conditions","volume":"10","author":"Wang","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jprot.2013.01.012","article-title":"Proteomic analysis of podocyte exosome-enriched fraction from normal human urine","volume":"82","author":"Prunotto","year":"2013","journal-title":"J. Proteom."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1530\/JOE-21-0228","article-title":"gammaENaC\/CD9 in urinary extracellular vesicles as a potential biomarker of MR activity","volume":"252","author":"Hayakawa","year":"2021","journal-title":"J. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hu, C.C., Katerelos, M., Choy, S.W., Crossthwaite, A., Walker, S.P., Pell, G., Lee, M., Cook, N., Mount, P.F., and Paizis, K. (2018). Pre-eclampsia is associated with altered expression of the renal sodium transporters NKCC2, NCC and ENaC in urinary extracellular vesicles. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204514"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"E47","DOI":"10.25011\/cim.v45i3.38876","article-title":"Significance of Mannan Binding Lectin-Associated Serine Protease 2 in Urinary Extracellular Vesicles in IgA Nephropathy","volume":"45","author":"Wu","year":"2022","journal-title":"Clin. Investig. Med."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/8\/1138\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:34:35Z","timestamp":1760128475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/8\/1138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,16]]},"references-count":92,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["biology12081138"],"URL":"https:\/\/doi.org\/10.3390\/biology12081138","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,16]]}}}