{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:08:15Z","timestamp":1786651695819,"version":"build-2736575974"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"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>The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1\u03b1 (SDF-1\u03b1), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy. DPP4-inhibitor (diprotin A or sitagliptin) increased the phosphorylation of Src and vascular endothelial-cadherin (VE-cadherin) in human endothelial cells and disrupted endothelial cell-to-cell junctions, which were attenuated by CXCR4 (receptor of SDF-1\u03b1)-blocker or Src-inhibitor. Disruption of endothelial cell-to-cell junctions in the immuno-fluorescence images correlated with the actual leakage of the endothelial monolayer in the transwell endothelial permeability assay. In the Miles assay, vascular leakage was observed in the ears into which SDF-1\u03b1 was injected, and this effect was aggravated by DPP4-inhibitor. In the model of retinopathy of prematurity, DPP4-inhibitor increased not only retinal vascularity but also leakage. Additionally, in the murine diabetic retinopathy model, DPP4-inhibitor increased the phosphorylation of Src and VE-cadherin and aggravated vascular leakage in the retinas. Collectively, DPP4-inhibitor induced vascular leakage by augmenting the SDF-1\u03b1\/CXCR4\/Src\/VE-cadherin signaling pathway. These data highlight safety issues associated with the use of DPP4-inhibitors.<\/jats:p>","DOI":"10.1038\/srep29393","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T10:19:01Z","timestamp":1467800341000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Dipeptidyl Peptidase-4 Inhibitor Increases Vascular Leakage in Retina through VE-cadherin Phosphorylation"],"prefix":"10.1038","volume":"6","author":[{"given":"Choon-Soo","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Gi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Jai","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonghanne","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heewon","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Pyo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Jae","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,6]]},"reference":[{"key":"BFsrep29393_CR1","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1056\/NEJMra1005073","volume":"366","author":"DA Antonetti","year":"2012","unstructured":"Antonetti, D. A., Klein, R. & Gardner, T. W. Diabetic retinopathy. N Engl J Med 366, 1227\u20131239 (2012).","journal-title":"N Engl J Med"},{"key":"BFsrep29393_CR2","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1172\/JCI22869","volume":"115","author":"JM Butler","year":"2005","unstructured":"Butler, J. M. et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest 115, 86\u201393 (2005).","journal-title":"J Clin Invest"},{"key":"BFsrep29393_CR3","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.bbamem.2006.11.002","volume":"1768","author":"JM Busillo","year":"2007","unstructured":"Busillo, J. M. & Benovic, J. L. Regulation of CXCR4 signaling. Biochim Biophys Acta 1768, 952\u2013963 (2007).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep29393_CR4","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1517\/14712598.2011.546338","volume":"11","author":"TT Lau","year":"2011","unstructured":"Lau, T. T. & Wang, D. A. Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine. Expert Opin Biol Ther 11, 189\u2013197 (2011).","journal-title":"Expert Opin Biol Ther"},{"key":"BFsrep29393_CR5","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.yjmcc.2015.01.024","volume":"81","author":"M Cheng","year":"2015","unstructured":"Cheng, M. et al. A critical role of Src family kinase in SDF-1\/CXCR4-mediated bone-marrow progenitor cell recruitment to the ischemic heart. J Mol Cell Cardiol 81, 49\u201353 (2015).","journal-title":"J Mol Cell Cardiol"},{"key":"BFsrep29393_CR6","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1161\/CIRCRESAHA.110.220970","volume":"107","author":"M Cheng","year":"2010","unstructured":"Cheng, M. et al. CXCR4-mediated bone marrow progenitor cell maintenance and mobilization are modulated by c-kit activity. Circ Res 107, 1083\u20131093 (2010).","journal-title":"Circ Res"},{"key":"BFsrep29393_CR7","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/S0092-8674(00)00086-6","volume":"102","author":"YC Ma","year":"2000","unstructured":"Ma, Y. C., Huang, J., Ali, S., Lowry, W. & Huang, X. Y. Src tyrosine kinase is a novel direct effector of G proteins. Cell 102, 635\u2013646 (2000).","journal-title":"Cell"},{"key":"BFsrep29393_CR8","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1038\/sj.onc.1209855","volume":"26","author":"Y Wallez","year":"2007","unstructured":"Wallez, Y. et al. Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site. Oncogene 26, 1067\u20131077 (2007).","journal-title":"Oncogene"},{"key":"BFsrep29393_CR9","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1161\/01.RES.0000156652.99586.9f","volume":"96","author":"N Lambeng","year":"2005","unstructured":"Lambeng, N. et al. Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues. Circ Res 96, 384\u2013391 (2005).","journal-title":"Circ Res"},{"key":"BFsrep29393_CR10","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1124\/mol.64.5.1029","volume":"64","author":"MT Lin","year":"2003","unstructured":"Lin, M. T., Yen, M. L., Lin, C. Y. & Kuo, M. L. Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol 64, 1029\u20131036 (2003).","journal-title":"Mol Pharmacol"},{"key":"BFsrep29393_CR11","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.tcm.2005.11.008","volume":"16","author":"Y Wallez","year":"2006","unstructured":"Wallez, Y., Vilgrain, I. & Huber, P. Angiogenesis: the VE-cadherin switch. Trends Cardiovasc Med 16, 55\u201359 (2006).","journal-title":"Trends Cardiovasc Med"},{"key":"BFsrep29393_CR12","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1161\/01.ATV.15.8.1229","volume":"15","author":"F Breviario","year":"1995","unstructured":"Breviario, F. et al. Functional properties of human vascular endothelial cadherin (7B4\/cadherin-5), an endothelium-specific cadherin. Arterioscler Thromb Vasc Biol 15, 1229\u20131239 (1995).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"BFsrep29393_CR13","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1242\/jcs.112.12.1915","volume":"112","author":"PL Hordijk","year":"1999","unstructured":"Hordijk, P. L. et al. Vascular-endothelial-cadherin modulates endothelial monolayer permeability. J Cell Sci 112 (Pt 12), 1915\u20131923 (1999).","journal-title":"J Cell Sci"},{"key":"BFsrep29393_CR14","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1182\/blood.V97.6.1679","volume":"97","author":"M Corada","year":"2001","unstructured":"Corada, M. et al. Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability. Blood 97, 1679\u20131684 (2001).","journal-title":"Blood"},{"key":"BFsrep29393_CR15","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1111\/j.1442-200X.2007.02491.x","volume":"49","author":"T Sasaki","year":"2007","unstructured":"Sasaki, T. et al. Stromal cell-derived factor-1alpha improves infarcted heart function through angiogenesis in mice. Pediatr Int 49, 966\u2013971 (2007).","journal-title":"Pediatr Int"},{"key":"BFsrep29393_CR16","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/S0140-6736(03)14232-8","volume":"362","author":"AT Askari","year":"2003","unstructured":"Askari, A. T. et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362, 697\u2013703 (2003).","journal-title":"Lancet"},{"key":"BFsrep29393_CR17","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1161\/CIRCRESAHA.108.186742","volume":"103","author":"H Haider","year":"2008","unstructured":"Haider, H., Jiang, S., Idris, N. M. & Ashraf, M. IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha\/CXCR4 signaling to promote myocardial repair. Circ Res 103, 1300\u20131308 (2008).","journal-title":"Circ Res"},{"key":"BFsrep29393_CR18","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.canlet.2013.03.005","volume":"335","author":"J Garcia-Roman","year":"2013","unstructured":"Garcia-Roman, J. & Zentella-Dehesa, A. Vascular permeability changes involved in tumor metastasis. Cancer Lett 335, 259\u2013269 (2013).","journal-title":"Cancer Lett"},{"key":"BFsrep29393_CR19","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1161\/CIRCULATIONAHA.105.589937","volume":"114","author":"D You","year":"2006","unstructured":"You, D. et al. Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy. Circulation 114, 328\u2013338 (2006).","journal-title":"Circulation"},{"key":"BFsrep29393_CR20","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.stem.2009.02.013","volume":"4","author":"MM Zaruba","year":"2009","unstructured":"Zaruba, M. M. et al. Synergy between CD26\/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell 4, 313\u2013323 (2009).","journal-title":"Cell Stem Cell"},{"key":"BFsrep29393_CR21","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.it.2008.02.010","volume":"29","author":"K Ohnuma","year":"2008","unstructured":"Ohnuma, K., Dang, N. H. & Morimoto, C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol 29, 295\u2013301 (2008).","journal-title":"Trends Immunol"},{"key":"BFsrep29393_CR22","doi-asserted-by":"publisher","first-page":"6331","DOI":"10.1073\/pnas.95.11.6331","volume":"95","author":"T Shioda","year":"1998","unstructured":"Shioda, T. et al. Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1alpha (SDF-1alpha) and SDF-1beta are abolished by CD26\/dipeptidyl peptidase IV-mediated cleavage. Proc Natl Acad Sci USA 95, 6331\u20136336 (1998).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep29393_CR23","doi-asserted-by":"publisher","first-page":"29839","DOI":"10.1074\/jbc.M103106200","volume":"276","author":"AM Lambeir","year":"2001","unstructured":"Lambeir, A. M. et al. Kinetic investigation of chemokine truncation by CD26\/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. J Biol Chem 276, 29839\u201329845 (2001).","journal-title":"J Biol Chem"},{"key":"BFsrep29393_CR24","doi-asserted-by":"publisher","first-page":"7000","DOI":"10.4049\/jimmunol.169.12.7000","volume":"169","author":"KW Christopherson 2nd","year":"2002","unstructured":"Christopherson, K. W., 2nd, Hangoc, G. & Broxmeyer, H. E. Cell surface peptidase CD26\/dipeptidylpeptidase IV regulates CXCL12\/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J Immunol 169, 7000\u20137008 (2002).","journal-title":"J Immunol"},{"key":"BFsrep29393_CR25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1182\/blood-2013-02-487470","volume":"122","author":"X Ou","year":"2013","unstructured":"Ou, X., O\u2019Leary, H. A. & Broxmeyer, H. E. Implications of DPP4 modification of proteins that regulate stem\/progenitor and more mature cell types. Blood 122, 161\u2013169 (2013).","journal-title":"Blood"},{"key":"BFsrep29393_CR26","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1093\/ejcts\/ezr180","volume":"41","author":"W Jungraithmayr","year":"2012","unstructured":"Jungraithmayr, W. et al. CD26\/DPP-4 inhibition recruits regenerative stem cells via stromal cell-derived factor-1 and beneficially influences ischaemia-reperfusion injury in mouse lung transplantation. Eur J Cardiothorac Surg 41, 1166\u20131173 (2012).","journal-title":"Eur J Cardiothorac Surg"},{"key":"BFsrep29393_CR27","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1161\/CIRCHEARTFAILURE.110.960302","volume":"4","author":"S Kanki","year":"2011","unstructured":"Kanki, S. et al. Stromal cell-derived factor-1 retention and cardioprotection for ischemic myocardium. Circ Heart Fail 4, 509\u2013518 (2011).","journal-title":"Circ Heart Fail"},{"key":"BFsrep29393_CR28","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.2337\/dc10-0187","volume":"33","author":"GP Fadini","year":"2010","unstructured":"Fadini, G. P. et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care 33, 1607\u20131609 (2010).","journal-title":"Diabetes Care"},{"key":"BFsrep29393_CR29","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1507\/endocrj.EJ13-0305","volume":"61","author":"H Fujita","year":"2014","unstructured":"Fujita, H. et al. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1alpha in type 2 diabetic patients with incipient nephropathy. Endocr J 61, 159\u2013166 (2014).","journal-title":"Endocr J"},{"key":"BFsrep29393_CR30","doi-asserted-by":"publisher","first-page":"25602","DOI":"10.1074\/jbc.M109.009894","volume":"284","author":"E Monaghan-Benson","year":"2009","unstructured":"Monaghan-Benson, E. & Burridge, K. The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen species. J Biol Chem 284, 25602\u201325611 (2009).","journal-title":"J Biol Chem"},{"key":"BFsrep29393_CR31","doi-asserted-by":"publisher","first-page":"31906","DOI":"10.1074\/jbc.M505568200","volume":"280","author":"MD Potter","year":"2005","unstructured":"Potter, M. D., Barbero, S. & Cheresh, D. A. Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state. J Biol Chem 280, 31906\u201331912 (2005).","journal-title":"J Biol Chem"},{"key":"BFsrep29393_CR32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.clinthera.2006.01.015","volume":"28","author":"AJ Bergman","year":"2006","unstructured":"Bergman, A. J. et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther 28, 55\u201372 (2006).","journal-title":"Clin Ther"},{"key":"BFsrep29393_CR33","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1083\/jcb.113.4.867","volume":"113","author":"S Tsukita","year":"1991","unstructured":"Tsukita, S. et al. Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated. J Cell Biol 113, 867\u2013879 (1991).","journal-title":"J Cell Biol"},{"key":"BFsrep29393_CR34","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1038\/sj.emboj.7600647","volume":"24","author":"U Baumeister","year":"2005","unstructured":"Baumeister, U. et al. Association of Csk to VE-cadherin and inhibition of cell proliferation. EMBO J 24, 1686\u20131695 (2005).","journal-title":"EMBO J"},{"key":"BFsrep29393_CR35","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.trsl.2012.12.008","volume":"161","author":"AA Birukova","year":"2013","unstructured":"Birukova, A. A. et al. Fragmented oxidation products define barrier disruptive endothelial cell response to OxPAPC. Transl Res 161, 495\u2013504 (2013).","journal-title":"Transl Res"},{"key":"BFsrep29393_CR36","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/ni.2824","volume":"15","author":"F Wessel","year":"2014","unstructured":"Wessel, F. et al. Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin. Nat Immunol 15, 223\u2013230 (2014).","journal-title":"Nat Immunol"},{"key":"BFsrep29393_CR37","doi-asserted-by":"publisher","first-page":"e4449","DOI":"10.1371\/journal.pone.0004449","volume":"4","author":"GC Alghisi","year":"2009","unstructured":"Alghisi, G. C., Ponsonnet, L. & Ruegg, C. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells. PLoS One 4, e4449 (2009).","journal-title":"PLoS One"},{"key":"BFsrep29393_CR38","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/nrneph.2013.275","volume":"10","author":"DG Warnock","year":"2014","unstructured":"Warnock, D. G. et al. Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells. Nat Rev Nephrol 10, 146\u2013157 (2014).","journal-title":"Nat Rev Nephrol"},{"key":"BFsrep29393_CR39","doi-asserted-by":"publisher","first-page":"e30957","DOI":"10.1371\/journal.pone.0030957","volume":"7","author":"AA Birukova","year":"2012","unstructured":"Birukova, A. A. et al. A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations. PLoS One 7, e30957 (2012).","journal-title":"PLoS One"},{"key":"BFsrep29393_CR40","doi-asserted-by":"publisher","first-page":"7045","DOI":"10.1074\/jbc.M109.079277","volume":"285","author":"AP Adam","year":"2010","unstructured":"Adam, A. P., Sharenko, A. L., Pumiglia, K. & Vincent, P. A. Src-induced tyrosine phosphorylation of VE-cadherin is not sufficient to decrease barrier function of endothelial monolayers. J Biol Chem 285, 7045\u20137055 (2010).","journal-title":"J Biol Chem"},{"key":"BFsrep29393_CR41","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/0022-4804(83)90034-3","volume":"35","author":"RH Bell Jr.","year":"1983","unstructured":"Bell, R. H., Jr. & Hye, R. J. Animal models of diabetes mellitus: physiology and pathology. J Surg Res 35, 433\u2013460 (1983).","journal-title":"J Surg Res"},{"key":"BFsrep29393_CR42","first-page":"101","volume":"35","author":"LE Smith","year":"1994","unstructured":"Smith, L. E. et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35, 101\u2013111 (1994).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"BFsrep29393_CR43","doi-asserted-by":"publisher","first-page":"456","DOI":"10.4103\/2249-4863.148149","volume":"3","author":"T Belice","year":"2014","unstructured":"Belice, T., Yuce, S., Kizilkaya, B., Kurt, A. & Cure, E. Noncardiac Pulmonary Edema induced by Sitagliptin Treatment. J Family Med Prim Care 3, 456\u2013457 (2014).","journal-title":"J Family Med Prim Care"},{"key":"BFsrep29393_CR44","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.2337\/dc11-1995","volume":"35","author":"K Yamauchi","year":"2012","unstructured":"Yamauchi, K. et al. RS3PE in association with dipeptidyl peptidase-4 inhibitor: report of two cases. Diabetes Care 35, e7 (2012).","journal-title":"Diabetes Care"},{"key":"BFsrep29393_CR45","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1161\/HYPERTENSIONAHA.107.096552","volume":"51","author":"JB Byrd","year":"2008","unstructured":"Byrd, J. B. et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension 51, 141\u2013147 (2008).","journal-title":"Hypertension"},{"key":"BFsrep29393_CR46","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.jaci.2007.04.012","volume":"120","author":"JB Byrd","year":"2007","unstructured":"Byrd, J. B. et al. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol 120, 403\u2013408 (2007).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep29393_CR47","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1111\/j.1365-2125.2010.03852.x","volume":"71","author":"GA Herman","year":"2011","unstructured":"Herman, G. A. et al. Evaluation of pharmacokinetic parameters and dipeptidyl peptidase-4 inhibition following single doses of sitagliptin in healthy, young Japanese males. Br J Clin Pharmacol 71, 429\u2013436 (2011).","journal-title":"Br J Clin Pharmacol"},{"key":"BFsrep29393_CR48","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.clinthera.2008.03.004","volume":"30","author":"P Covington","year":"2008","unstructured":"Covington, P. et al. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther 30, 499\u2013512 (2008).","journal-title":"Clin Ther"},{"key":"BFsrep29393_CR49","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.clinthera.2008.03.005","volume":"30","author":"R Christopher","year":"2008","unstructured":"Christopher, R. et al. Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects. Clin Ther 30, 513\u2013527 (2008).","journal-title":"Clin Ther"},{"key":"BFsrep29393_CR50","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.exphem.2011.10.010","volume":"40","author":"E Schwaiger","year":"2012","unstructured":"Schwaiger, E. et al. Dipeptidyl peptidase IV (DPPIV\/CD26) inhibition does not improve engraftment of unfractionated syngeneic or allogeneic bone marrow after nonmyeloablative conditioning. Exp Hematol 40, 97\u2013106 (2012).","journal-title":"Exp Hematol"},{"key":"BFsrep29393_CR51","doi-asserted-by":"publisher","first-page":"H1339","DOI":"10.1152\/ajpheart.00592.2010","volume":"299","author":"D Zhang","year":"2010","unstructured":"Zhang, D. et al. Genetically manipulated progenitor cell sheet with diprotin A improves myocardial function and repair of infarcted hearts. Am J Physiol Heart Circ Physiol 299, H1339\u20131347 (2010).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"BFsrep29393_CR52","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1126\/science.1097071","volume":"305","author":"KW Christopherson 2nd","year":"2004","unstructured":"Christopherson, K. W., 2nd, Hangoc, G., Mantel, C. R. & Broxmeyer, H. E. Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 305, 1000\u20131003 (2004).","journal-title":"Science"},{"key":"BFsrep29393_CR53","doi-asserted-by":"publisher","first-page":"132","DOI":"10.4103\/0022-3859.97176","volume":"58","author":"B Kumar","year":"2012","unstructured":"Kumar, B., Gupta, S. K., Saxena, R. & Srivastava, S. Current trends in the pharmacotherapy of diabetic retinopathy. J Postgrad Med 58, 132\u2013139 (2012).","journal-title":"J Postgrad Med"},{"key":"BFsrep29393_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1350-9462(02)00043-5","volume":"22","author":"AN Witmer","year":"2003","unstructured":"Witmer, A. N., Vrensen, G. F., Van Noorden, C. J. & Schlingemann, R. O. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 22, 1\u201329 (2003).","journal-title":"Prog Retin Eye Res"},{"key":"BFsrep29393_CR55","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.ophtha.2010.03.045","volume":"117","author":"M Michaelides","year":"2010","unstructured":"Michaelides, M. et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 117, 1078\u20131086 e1072 (2010).","journal-title":"Ophthalmology"},{"key":"BFsrep29393_CR56","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1161\/CIRCRESAHA.109.201673","volume":"105","author":"Y Sun","year":"2009","unstructured":"Sun, Y., Hu, G., Zhang, X. & Minshall, R. D. Phosphorylation of caveolin-1 regulates oxidant-induced pulmonary vascular permeability via paracellular and transcellular pathways. Circ Res 105, 676\u2013685, 615 p following 685 (2009).","journal-title":"Circ Res"},{"key":"BFsrep29393_CR57","doi-asserted-by":"publisher","first-page":"e73407","DOI":"10.1371\/journal.pone.0073407","volume":"8","author":"T Mammoto","year":"2013","unstructured":"Mammoto, T. et al. Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema by altering Tie2 expression. PLoS One 8, e73407 (2013).","journal-title":"PLoS One"},{"key":"BFsrep29393_CR58","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.2119\/molmed.2011.00106","volume":"17","author":"SW Lee","year":"2011","unstructured":"Lee, S. W. et al. Angiopoietin-1 protects heart against ischemia\/reperfusion injury through VE-cadherin dephosphorylation and myocardiac integrin-beta1\/ERK\/caspase-9 phosphorylation cascade. Mol Med 17, 1095\u20131106 (2011).","journal-title":"Mol Med"},{"key":"BFsrep29393_CR59","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1113\/jphysiol.2012.237834","volume":"591","author":"M Aslam","year":"2013","unstructured":"Aslam, M. et al. Hypoxia-reoxygenation-induced endothelial barrier failure: role of RhoA, Rac1 and myosin light chain kinase. J Physiol 591, 461\u2013473 (2013).","journal-title":"J Physiol"},{"key":"BFsrep29393_CR60","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/BF02623441","volume":"22","author":"H Hoshi","year":"1986","unstructured":"Hoshi, H. & McKeehan, W. L. Isolation, growth requirements, cloning, prostacyclin production and life-span of human adult endothelial cells in low serum culture medium. In Vitro Cell Dev Biol 22, 51\u201356 (1986).","journal-title":"In Vitro Cell Dev Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep29393.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29393","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29393.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:51:38Z","timestamp":1672901498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep29393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,6]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,29]]}},"alternative-id":["BFsrep29393"],"URL":"https:\/\/doi.org\/10.1038\/srep29393","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,6]]},"assertion":[{"value":"15 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29393"}}