{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:09:13Z","timestamp":1794254953345,"version":"4.9.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A host of hormonal-metabolic alterations take place following exposure of cardiomyocytes to hypoxia and other noxious stimuli. Here, we demonstrate that exposure of cultured rat cardiomyocytes to lipopolysaccharide (LPS) resulted in upregulation (~1.5 fold) of oxidized low-density lipoprotein receptor-1 (LOX-1). There was also a marked increase in apoptosis 12 hrs after LPS treatment with caspase-3 levels being significantly elevated (~1.3 fold) and a significant increase in LDH release at 24 hrs. Interestingly, there was a ~1.4-fold upregulation of LC-3 expression post-LPS treatment indicating development of autophagy, which probably is a compensatory response to combat cellular injury induced by LPS. Treatment with LPS also reduced the size and morphology of cardiomyocyte spheroids. In an attempt to limit LPS-induced injury, cardiomyocytes were treated with exosomes derived from mesenchymal stromal cells (MSCs). We noted a significant suppression of LOX-1 expression that in turn suppressed apoptosis as well as autophagic response and restored spheroid morphology. Mass spectrophotometric analysis of MSC exosomes revealed a cargo rich in proteins which are involved in pathways negatively modulating cell death and apoptosis while promoting cell survival. This is first report to our knowledge on the initial molecular events in MSC exosome mediated cytoprotection of stressed cardiomyocytes.<\/jats:p>","DOI":"10.1038\/s41598-019-55694-7","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T11:02:49Z","timestamp":1576580569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Molecular events in MSC exosome mediated cytoprotection in cardiomyocytes"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9764-3317","authenticated-orcid":false,"given":"Rajshekhar A.","family":"Kore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Henson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabab N.","family":"Hamzah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Tackett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zufeng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawahar L.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"55694_CR1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1161\/01.cir.0000442015.53336.12","volume":"129","author":"AS Go","year":"2014","unstructured":"Go, A. S. et al. Executive summary: heart disease and stroke statistics\u20132014 update: a report from the American Heart Association. Circulation 129, 399\u2013410, https:\/\/doi.org\/10.1161\/01.cir.0000442015.53336.12 (2014).","journal-title":"Circulation"},{"key":"55694_CR2","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/S0008-6363(99)00348-X","volume":"45","author":"HN Sabbah","year":"2000","unstructured":"Sabbah, H. N. Apoptotic cell death in heart failure. Cardiovascular research 45, 704\u2013712, https:\/\/doi.org\/10.1016\/S0008-6363(99)00348-X (2000).","journal-title":"Cardiovascular research"},{"key":"55694_CR3","doi-asserted-by":"publisher","unstructured":"Wang, X., Guo, Z., Ding, Z. & Mehta, J. L. Inflammation, autophagy, and apoptosis after myocardial infarction. J Am Heart Assoc 7, https:\/\/doi.org\/10.1161\/jaha.117.008024 (2018).","DOI":"10.1161\/jaha.117.008024"},{"key":"55694_CR4","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1161\/01.RES.66.4.1133","volume":"66","author":"RJ Schott","year":"1990","unstructured":"Schott, R. J., Rohmann, S., Braun, E. R. & Schaper, W. Ischemic preconditioning reduces infarct size in swine myocardium. Circulation research 66, 1133\u20131142 (1990).","journal-title":"Circulation research"},{"key":"55694_CR5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s11010-009-0377-x","volume":"339","author":"C Wagner","year":"2010","unstructured":"Wagner, C., Tillack, D., Simonis, G., Strasser, R. H. & Weinbrenner, C. Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of PI3-K, mTOR, GSK-3\u03b2, and apoptosis. Molecular and Cellular Biochemistry 339, 135\u2013147, https:\/\/doi.org\/10.1007\/s11010-009-0377-x (2010).","journal-title":"Molecular and Cellular Biochemistry"},{"key":"55694_CR6","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s12265-010-9189-3","volume":"3","author":"C Huang","year":"2010","unstructured":"Huang, C. et al. Autophagy induced by ischemic preconditioning is essential for cardioprotection. Journal of cardiovascular translational research 3, 365\u2013373, https:\/\/doi.org\/10.1007\/s12265-010-9189-3 (2010).","journal-title":"Journal of cardiovascular translational research"},{"key":"55694_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.lfs.2017.07.035","volume":"186","author":"Z Giricz","year":"2017","unstructured":"Giricz, Z. et al. Autophagosome formation is required for cardioprotection by chloramphenicol. Life sciences 186, 11\u201316, https:\/\/doi.org\/10.1016\/j.lfs.2017.07.035 (2017).","journal-title":"Life sciences"},{"key":"55694_CR8","doi-asserted-by":"publisher","first-page":"3851","DOI":"10.1210\/en.2006-0088","volume":"147","author":"N Duerrschmidt","year":"2006","unstructured":"Duerrschmidt, N. et al. Lectin-like oxidized low-density lipoprotein receptor-1-mediated autophagy in human granulosa cells as an alternative of programmed cell death. Endocrinology 147, 3851\u20133860, https:\/\/doi.org\/10.1210\/en.2006-0088 (2006).","journal-title":"Endocrinology"},{"key":"55694_CR9","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1161\/01.RES.83.3.322","volume":"83","author":"N Kume","year":"1998","unstructured":"Kume, N. et al. Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circulation research 83, 322\u2013327 (1998).","journal-title":"Circulation research"},{"key":"55694_CR10","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1161\/01.RES.84.9.1043","volume":"84","author":"DY Li","year":"1999","unstructured":"Li, D. Y., Zhang, Y. C., Philips, M. I., Sawamura, T. & Mehta, J. L. Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation. Circulation research 84, 1043\u20131049 (1999).","journal-title":"Circulation research"},{"key":"55694_CR11","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.cardiores.2005.09.006","volume":"69","author":"J Chen","year":"2006","unstructured":"Chen, J., Hermonat, P. L., Mehta, J. L., Romeo, F. & Novelli, G. Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): A critical player in the development of atherosclerosis and related disorders. Cardiovascular research 69, 36\u201345, https:\/\/doi.org\/10.1016\/j.cardiores.2005.09.006 (2006).","journal-title":"Cardiovascular research"},{"key":"55694_CR12","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/gt.2011.133","volume":"19","author":"J Lu","year":"2012","unstructured":"Lu, J. et al. LOX-1 abrogation reduces cardiac hypertrophy and collagen accumulation following chronic ischemia in the mouse. Gene therapy 19, 522\u2013531, https:\/\/doi.org\/10.1038\/gt.2011.133 (2012).","journal-title":"Gene therapy"},{"key":"55694_CR13","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1093\/cvr\/cvu114","volume":"103","author":"Z Ding","year":"2014","unstructured":"Ding, Z. et al. LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis. Cardiovascular research 103, 619\u2013628, https:\/\/doi.org\/10.1093\/cvr\/cvu114 (2014).","journal-title":"Cardiovascular research"},{"key":"55694_CR14","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s10557-014-6541-x","volume":"28","author":"X Wang","year":"2014","unstructured":"Wang, X. et al. LOX-1 deletion limits cardiac angiogenesis in mice given angiotensin II. Cardiovasc Drugs Ther 28, 441\u2013446, https:\/\/doi.org\/10.1007\/s10557-014-6541-x (2014).","journal-title":"Cardiovasc Drugs Ther"},{"key":"55694_CR15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/path.2697","volume":"221","author":"D Glick","year":"2010","unstructured":"Glick, D., Barth, S. & Macleod, K. F. Autophagy: cellular and molecular mechanisms. J Pathol 221, 3\u201312, https:\/\/doi.org\/10.1002\/path.2697 (2010).","journal-title":"J Pathol"},{"issue":"2","key":"55694_CR16","doi-asserted-by":"publisher","first-page":"117","DOI":"10.2174\/1574888X13666180502103831","volume":"14","author":"Tapan Kumar Giri","year":"2019","unstructured":"Giri, T. K. et al. Current status of stem cell therapies in tissue repair and regeneration. Current stem cell research & therapy, https:\/\/doi.org\/10.2174\/1574888x13666180502103831 (2018).","journal-title":"Current Stem Cell Research & Therapy"},{"issue":"11","key":"55694_CR17","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/s41569-018-0013-0","volume":"15","author":"Philippe Menasch\u00e9","year":"2018","unstructured":"Menasche, P. Cell therapy trials for heart regeneration - lessons learned and future directions. Nature reviews. Cardiology, https:\/\/doi.org\/10.1038\/s41569-018-0013-0 (2018).","journal-title":"Nature Reviews Cardiology"},{"key":"55694_CR18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41551-017-0182-x","volume":"2","author":"J Tang","year":"2018","unstructured":"Tang, J. et al. Targeted repair of heart injury by stem cells fused with platelet nanovesicles. Nature biomedical engineering 2, 17\u201326, https:\/\/doi.org\/10.1038\/s41551-017-0182-x (2018).","journal-title":"Nature biomedical engineering"},{"key":"55694_CR19","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1161\/circresaha.117.312486","volume":"122","author":"BA Tompkins","year":"2018","unstructured":"Tompkins, B. A. et al. Preclinical Studies of Stem Cell Therapy for Heart Disease. Circ Res 122, 1006\u20131020, https:\/\/doi.org\/10.1161\/circresaha.117.312486 (2018).","journal-title":"Circ Res"},{"issue":"4","key":"55694_CR20","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s10557-018-6804-z","volume":"32","author":"Su Hyun Kim","year":"2018","unstructured":"Kim, S. H. et al. Improvement in Left Ventricular Function with Intracoronary Mesenchymal Stem Cell Therapy in a Patient with Anterior Wall ST-Segment Elevation Myocardial Infarction. Cardiovascular drugs and therapy, https:\/\/doi.org\/10.1007\/s10557-018-6804-z (2018).","journal-title":"Cardiovascular Drugs and Therapy"},{"key":"55694_CR21","doi-asserted-by":"publisher","first-page":"259","DOI":"10.23736\/s0021-9509.17.10126-6","volume":"59","author":"G Laguna","year":"2018","unstructured":"Laguna, G. et al. Effect of direct intramyocardial autologous stem cell grafting in the sub-acute phase after myocardial infarction. The Journal of cardiovascular surgery 59, 259\u2013267, https:\/\/doi.org\/10.23736\/s0021-9509.17.10126-6 (2018).","journal-title":"The Journal of cardiovascular surgery"},{"key":"55694_CR22","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1159\/000477324","volume":"42","author":"CI Lang","year":"2017","unstructured":"Lang, C. I. et al. Cardiac Cell Therapies for the Treatment of Acute Myocardial Infarction: A Meta-Analysis from Mouse Studies. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology 42, 254\u2013268, https:\/\/doi.org\/10.1159\/000477324 (2017).","journal-title":"Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology"},{"key":"55694_CR23","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1016\/j.ymthe.2018.04.024","volume":"26","author":"M Adamiak","year":"2018","unstructured":"Adamiak, M. & Sahoo, S. Exosomes in Myocardial Repair: Advances and Challenges in the Development of Next-Generation Therapeutics. Molecular therapy: the journal of the American Society of Gene Therapy 26, 1635\u20131643, https:\/\/doi.org\/10.1016\/j.ymthe.2018.04.024 (2018).","journal-title":"Molecular therapy: the journal of the American Society of Gene Therapy"},{"key":"55694_CR24","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1016\/j.ymthe.2018.05.009","volume":"26","author":"L Bagno","year":"2018","unstructured":"Bagno, L., Hatzistergos, K. E., Balkan, W. & Hare, J. M. Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges. Molecular therapy: the journal of the American Society of Gene Therapy 26, 1610\u20131623, https:\/\/doi.org\/10.1016\/j.ymthe.2018.05.009 (2018).","journal-title":"Molecular therapy: the journal of the American Society of Gene Therapy"},{"key":"55694_CR25","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1161\/circresaha.117.311215","volume":"123","author":"VNS Garikipati","year":"2018","unstructured":"Garikipati, V. N. S., Shoja-Taheri, F., Davis, M. E. & Kishore, R. Extracellular Vesicles and the Application of System Biology and Computational Modeling in Cardiac Repair. Circulation research 123, 188\u2013204, https:\/\/doi.org\/10.1161\/circresaha.117.311215 (2018).","journal-title":"Circulation research"},{"key":"55694_CR26","doi-asserted-by":"publisher","unstructured":"Gartz, M. & Strande, J. L. Examining the Paracrine Effects of Exosomes in Cardiovascular Disease and Repair. Journal of the American Heart Association 7, https:\/\/doi.org\/10.1161\/jaha.117.007954 (2018).","DOI":"10.1161\/jaha.117.007954"},{"key":"55694_CR27","doi-asserted-by":"publisher","first-page":"547","DOI":"10.3389\/fphar.2018.00547","volume":"9","author":"Y Yuan","year":"2018","unstructured":"Yuan, Y. et al. Stem Cell-Derived Exosome in Cardiovascular Diseases: Macro Roles of Micro Particles. Frontiers in pharmacology 9, 547, https:\/\/doi.org\/10.3389\/fphar.2018.00547 (2018).","journal-title":"Frontiers in pharmacology"},{"issue":"12","key":"55694_CR28","doi-asserted-by":"publisher","first-page":"21732","DOI":"10.1002\/jcp.28894","volume":"234","author":"Jafar Rezaie","year":"2019","unstructured":"Rezaie, J. et al. Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases. Journal of cellular physiology, https:\/\/doi.org\/10.1002\/jcp.28894 (2019).","journal-title":"Journal of Cellular Physiology"},{"key":"55694_CR29","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1038\/mt.2010.105","volume":"18","author":"D Sun","year":"2010","unstructured":"Sun, D. et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Molecular therapy: the journal of the American Society of Gene Therapy 18, 1606\u20131614, https:\/\/doi.org\/10.1038\/mt.2010.105 (2010).","journal-title":"Molecular therapy: the journal of the American Society of Gene Therapy"},{"key":"55694_CR30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/7651_2018_187","volume-title":"Stem Cell Niche","author":"Madeline Campbell","year":"2018","unstructured":"Campbell, M., Chabria, M., Figtree, G. A., Polonchuk, L. & Gentile, C. Stem Cell-Derived Cardiac Spheroids as 3D In Vitro Models of the Human Heart Microenvironment. Methods in molecular biology (Clifton, N.J.), https:\/\/doi.org\/10.1007\/7651_2018_187 (2018)."},{"issue":"2","key":"55694_CR31","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3390\/bioengineering5020036","volume":"5","author":"Jonas Christoffersson","year":"2018","unstructured":"Christoffersson, J., Meier, F. & Kempf, H. A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device. 5, https:\/\/doi.org\/10.3390\/bioengineering5020036 (2018).","journal-title":"Bioengineering"},{"issue":"1","key":"55694_CR32","doi-asserted-by":"publisher","first-page":"1321455","DOI":"10.1080\/20013078.2017.1321455","volume":"6","author":"Mohashin Pathan","year":"2017","unstructured":"Pathan, M. & Keerthikumar, S. A novel community driven software for functional enrichment analysis of extracellular vesicles data. 6, 1321455, https:\/\/doi.org\/10.1080\/20013078.2017.1321455 (2017).","journal-title":"Journal of Extracellular Vesicles"},{"key":"55694_CR33","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kramer","year":"2014","unstructured":"Kramer, A., Green, J., Pollard, J. Jr. & Tugendreich, S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics (Oxford, England) 30, 523\u2013530, https:\/\/doi.org\/10.1093\/bioinformatics\/btt703 (2014).","journal-title":"Bioinformatics (Oxford, England)"},{"key":"55694_CR34","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.bbrc.2014.09.068","volume":"453","author":"RA Kore","year":"2014","unstructured":"Kore, R. A. & Abraham, E. C. Inflammatory cytokines, interleukin-1 beta and tumor necrosis factor-alpha, upregulated in glioblastoma multiforme, raise the levels of CRYAB in exosomes secreted by U373 glioma cells. Biochem Biophys Res Commun 453, 326\u2013331, https:\/\/doi.org\/10.1016\/j.bbrc.2014.09.068 (2014).","journal-title":"Biochem Biophys Res Commun"},{"key":"55694_CR35","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.bbrep.2018.03.008","volume":"14","author":"RA Kore","year":"2018","unstructured":"Kore, R. A. et al. Hypoxia-derived exosomes induce putative altered pathways in biosynthesis and ion regulatory channels in glioblastoma cells. Biochem Biophys Rep 14, 104\u2013113, https:\/\/doi.org\/10.1016\/j.bbrep.2018.03.008 (2018).","journal-title":"Biochem Biophys Rep"},{"key":"55694_CR36","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1258\/ebm.2012.012212","volume":"237","author":"X Wang","year":"2012","unstructured":"Wang, X. et al. Cross-talk between inflammation and angiotensin II: studies based on direct transfection of cardiomyocytes with AT1R and AT2R cDNA. Experimental biology and medicine (Maywood, N.J.) 237, 1394\u20131401, https:\/\/doi.org\/10.1258\/ebm.2012.012212 (2012).","journal-title":"Experimental biology and medicine (Maywood, N.J.)"},{"key":"55694_CR37","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/S0735-1097(02)02966-2","volume":"41","author":"D Li","year":"2003","unstructured":"Li, D. et al. Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction. Journal of the American College of Cardiology 41, 1048\u20131055 (2003).","journal-title":"Journal of the American College of Cardiology"},{"key":"55694_CR38","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.yjmcc.2007.10.009","volume":"44","author":"C Hu","year":"2008","unstructured":"Hu, C. et al. LOX-1 abrogation reduces myocardial ischemia-reperfusion injury in mice. Journal of molecular and cellular cardiology 44, 76\u201383, https:\/\/doi.org\/10.1016\/j.yjmcc.2007.10.009 (2008).","journal-title":"Journal of molecular and cellular cardiology"},{"key":"55694_CR39","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1016\/j.ijcard.2012.12.045","volume":"168","author":"Z Ding","year":"2013","unstructured":"Ding, Z. et al. Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7 g. International journal of cardiology 168, 1378\u20131385, https:\/\/doi.org\/10.1016\/j.ijcard.2012.12.045 (2013).","journal-title":"International journal of cardiology"},{"key":"55694_CR40","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/cdd.2008.51","volume":"15","author":"F Scarlatti","year":"2008","unstructured":"Scarlatti, F., Maffei, R., Beau, I., Codogno, P. & Ghidoni, R. Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell death and differentiation 15, 1318\u20131329, https:\/\/doi.org\/10.1038\/cdd.2008.51 (2008).","journal-title":"Cell death and differentiation"},{"key":"55694_CR41","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.4161\/auto.6.8.13336","volume":"6","author":"S Tian","year":"2010","unstructured":"Tian, S. et al. Beclin 1-independent autophagy induced by a Bcl-XL\/Bcl-2 targeting compound, Z18. Autophagy 6, 1032\u20131041, https:\/\/doi.org\/10.4161\/auto.6.8.13336 (2010).","journal-title":"Autophagy"},{"key":"55694_CR42","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-015-0182-y","volume":"8","author":"RJM Correa","year":"2015","unstructured":"Correa, R. J. M., Valdes, Y. R., Shepherd, T. G. & DiMattia, G. E. Beclin-1 expression is retained in high-grade serous ovarian cancer yet is not essential for autophagy induction in vitro. Journal of Ovarian Research 8, 52, https:\/\/doi.org\/10.1186\/s13048-015-0182-y (2015).","journal-title":"Journal of Ovarian Research"},{"key":"55694_CR43","doi-asserted-by":"publisher","first-page":"3200","DOI":"10.1038\/s41419-017-0041-4","volume":"8","author":"X Yuan","year":"2017","unstructured":"Yuan, X. et al. Extracellular vesicles from human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs) protect against renal ischemia\/reperfusion injury via delivering specificity protein (SP1) and transcriptional activating of sphingosine kinase 1 and inhibiting necroptosis. Cell Death & Disease 8, 3200, https:\/\/doi.org\/10.1038\/s41419-017-0041-4 (2017).","journal-title":"Cell Death & Disease"},{"key":"55694_CR44","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1006\/dbio.2001.0243","volume":"233","author":"F Laub","year":"2001","unstructured":"Laub, F. et al. Developmental Expression of Mouse Kr\u00fcppel-like Transcription Factor KLF7 Suggests a Potential Role in Neurogenesis. Developmental Biology 233, 305\u2013318, https:\/\/doi.org\/10.1006\/dbio.2001.0243 (2001).","journal-title":"Developmental Biology"},{"key":"55694_CR45","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s13353-016-0355-4","volume":"58","author":"AF Vega-Benedetti","year":"2017","unstructured":"Vega-Benedetti, A. F. et al. PLAGL1: an important player in diverse pathological processes. Journal of applied genetics 58, 71\u201378, https:\/\/doi.org\/10.1007\/s13353-016-0355-4 (2017).","journal-title":"Journal of applied genetics"},{"key":"55694_CR46","doi-asserted-by":"publisher","first-page":"10466","DOI":"10.1093\/nar\/gkx672","volume":"45","author":"A Varrault","year":"2017","unstructured":"Varrault, A. et al. Identification of Plagl1\/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network. Nucleic acids research 45, 10466\u201310480, https:\/\/doi.org\/10.1093\/nar\/gkx672 (2017).","journal-title":"Nucleic acids research"},{"key":"55694_CR47","doi-asserted-by":"publisher","first-page":"769","DOI":"10.2217\/bmm.13.63","volume":"7","author":"F Properzi","year":"2013","unstructured":"Properzi, F., Logozzi, M. & Fais, S. Exosomes: the future of biomarkers in medicine. Biomarkers in medicine 7, 769\u2013778, https:\/\/doi.org\/10.2217\/bmm.13.63 (2013).","journal-title":"Biomarkers in medicine"},{"key":"55694_CR48","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1002\/prca.201400114","volume":"9","author":"S Boukouris","year":"2015","unstructured":"Boukouris, S. & Mathivanan, S. Exosomes in bodily fluids are a highly stable resource of disease biomarkers. Proteomics. Clinical applications 9, 358\u2013367, https:\/\/doi.org\/10.1002\/prca.201400114 (2015).","journal-title":"Proteomics. Clinical applications"},{"key":"55694_CR49","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00018-014-1764-3","volume":"72","author":"LT Brinton","year":"2015","unstructured":"Brinton, L. T., Sloane, H. S., Kester, M. & Kelly, K. A. Formation and role of exosomes in cancer. Cellular and molecular life sciences: CMLS 72, 659\u2013671, https:\/\/doi.org\/10.1007\/s00018-014-1764-3 (2015).","journal-title":"Cellular and molecular life sciences: CMLS"},{"key":"55694_CR50","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1146\/annurev-physiol-021014-071641","volume":"77","author":"S Kourembanas","year":"2015","unstructured":"Kourembanas, S. Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. Annual review of physiology 77, 13\u201327, https:\/\/doi.org\/10.1146\/annurev-physiol-021014-071641 (2015).","journal-title":"Annual review of physiology"},{"key":"55694_CR51","doi-asserted-by":"publisher","first-page":"657086","DOI":"10.1155\/2015\/657086","volume":"2015","author":"J Lin","year":"2015","unstructured":"Lin, J. et al. Exosomes: novel biomarkers for clinical diagnosis. TheScientificWorldJournal 2015, 657086, https:\/\/doi.org\/10.1155\/2015\/657086 (2015).","journal-title":"TheScientificWorldJournal"},{"key":"55694_CR52","doi-asserted-by":"publisher","first-page":"e0170628","DOI":"10.1371\/journal.pone.0170628","volume":"12","author":"I Helwa","year":"2017","unstructured":"Helwa, I. et al. A Comparative Study of Serum Exosome Isolation Using Differential Ultracentrifugation and Three Commercial Reagents. PloS one 12, e0170628, https:\/\/doi.org\/10.1371\/journal.pone.0170628 (2017).","journal-title":"PloS one"},{"key":"55694_CR53","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.bbamcr.2015.11.027","volume":"1863","author":"RA Kore","year":"2016","unstructured":"Kore, R. A. & Abraham, E. C. Phosphorylation negatively regulates exosome mediated secretion of cryAB in glioma cells. Biochim Biophys Acta 1863, 368\u2013377, https:\/\/doi.org\/10.1016\/j.bbamcr.2015.11.027 (2016).","journal-title":"Biochim Biophys Acta"},{"key":"55694_CR54","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1021\/ac0341261","volume":"75","author":"AI Nesvizhskii","year":"2003","unstructured":"Nesvizhskii, A. I., Keller, A., Kolker, E. & Aebersold, R. A statistical model for identifying proteins by tandem mass spectrometry. Analytical chemistry 75, 4646\u20134658 (2003).","journal-title":"Analytical chemistry"}],"updated-by":[{"DOI":"10.1038\/s41598-022-11690-y","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55694-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55694-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55694-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T17:30:19Z","timestamp":1671298219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55694-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,17]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["55694"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-55694-7","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41598-022-11690-y","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,17]]},"assertion":[{"value":"27 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-022-11690-y","URL":"https:\/\/doi.org\/10.1038\/s41598-022-11690-y","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19276"}}