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By generating a potentially novel endothelial specific\n                    <jats:italic>Dgke<\/jats:italic>\n                    -knockout mouse, we demonstrate that loss of\n                    <jats:italic>Dgke<\/jats:italic>\n                    in the endothelium results in impaired signaling downstream of VEGFR2 due to cellular shortage of phosphatidylinositol 4,5-biphosphate. Mechanistically, we found that, in the absence of DGK\u03b5 in the endothelium, Akt fails to be activated upon VEGFR2 stimulation, resulting in defective induction of the enzyme cyclooxygenase 2 and production of prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ). Treating the endothelial specific\n                    <jats:italic>Dgke<\/jats:italic>\n                    -knockout mice with a stable PGE\n                    <jats:sub>2<\/jats:sub>\n                    analog was sufficient to reverse the clinical manifestations of thrombotic microangiopathy and proteinuria, possibly by suppressing the expression of matrix metalloproteinase 2 through PGE\n                    <jats:sub>2<\/jats:sub>\n                    -dependent upregulation of the chemokine receptor CXCR4. Our study reveals a complex array of autocrine signaling events downstream of VEGFR2 that are mediated by PGE\n                    <jats:sub>2<\/jats:sub>\n                    , that control endothelial activation and thrombogenic state, and that result in abnormalities of the glomerular filtration barrier.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.146959","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T14:01:18Z","timestamp":1620568878000},"source":"Crossref","is-referenced-by-count":24,"title":["Loss of diacylglycerol kinase \u03b5 causes thrombotic microangiopathy by impairing endothelial VEGFA signaling"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7581-2527","authenticated-orcid":true,"given":"Dingxiao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."},{"name":"Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-321X","authenticated-orcid":true,"given":"Dao-Fu","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswajit","family":"Padhy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasa K.","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Purvis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-1187","authenticated-orcid":true,"given":"Heng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil K.","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chou-Long","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Attanasio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0902814"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012090903"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2590"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.17.10237"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1021\/bi800492c"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.081536298"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1021\/bi901551e"},{"key":"B8","doi-asserted-by":"crossref","unstructured":"So V, et al. 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