{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:43:20Z","timestamp":1793371400631,"version":"4.5.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              TFEB (transcription factor EB) was recently reported to be induced by atheroprotective laminar flow and play an anti-atherosclerotic role by inhibiting inflammation in endothelial cells (ECs). This study aims to investigate whether TFEB regulates endothelial inflammation in diabetic\n              <jats:italic>db\/db<\/jats:italic>\n              mice and the molecular mechanisms involved.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Endothelial denudation shows that TFEB is mainly expressed in ECs in mouse aortas. Western blotting shows TFEB total protein level decreases whereas the p-TFEB S142 (phosphorylated form of TFEB) increases in\n              <jats:italic>db\/db<\/jats:italic>\n              mouse aortas, suggesting a decreased TFEB activity. Adenoviral TFEB overexpression reduces endothelial inflammation as evidenced by decreased expression of vascular inflammatory markers in\n              <jats:italic>db\/db<\/jats:italic>\n              mouse aortas, and reduced expression of a wide range of adhesion molecules and chemokines in human umbilical vein ECs. Monocyte attachment assay shows TFEB suppresses monocyte adhesion to human umbilical vein ECs. RNA sequencing of TFEB-overexpressed human umbilical vein ECs suggested TFEB inhibits NF-\u03baB (nuclear factor-kappa B) signaling. Indeed, luciferase assay shows TFEB suppresses NF-\u03baB transcriptional activity. Mechanistically, TFEB suppresses IKK (I\u03baB kinase) activity to protect I\u03baB-\u03b1 from degradation, leading to reduced p65 nuclear translocation. Inhibition of IKK by PS-1145 abolished TFEB silencing-induced inflammation in human umbilical vein ECs. Lastly, we identified KLF2 (Kr\u00fcppel-like factor 2) upregulates TFEB expression and promoter activity. Laminar flow experiment showed that KLF2 is required for TFEB induction by laminar flow and TFEB is an anti-inflammatory effector downstream of laminar flow-KLF2 signaling in ECs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>These findings suggest that TFEB exerts anti-inflammatory effects in diabetic mice and such function in ECs is achieved by inhibiting IKK activity and increasing I\u03baB\u03b1 level to suppress NF-\u03baB activity. KLF2 mediates TFEB upregulation in response to laminar flow.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.119.312316","type":"journal-article","created":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T14:40:00Z","timestamp":1551364800000},"page":"719-730","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Endothelial TFEB (Transcription Factor EB) Restrains IKK (I\u03baB Kinase)-p65 Pathway to Attenuate Vascular Inflammation in Diabetic\n            <i>db\/db<\/i>\n            Mice"],"prefix":"10.1161","volume":"39","author":[{"given":"Wencong","family":"Song","sequence":"first","affiliation":[{"name":"From the Institute of Vascular Medicine, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L., Y.H.)"},{"name":"School of Biomedical Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L.,Y.H.), Chinese University of Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Institute of Vascular Medicine, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L., Y.H.)"},{"name":"School of Biomedical Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L.,Y.H.), Chinese University of Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingshan","family":"Gou","sequence":"additional","affiliation":[{"name":"From the Institute of Vascular Medicine, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L., Y.H.)"},{"name":"School of Biomedical Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L.,Y.H.), Chinese University of Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"He","sequence":"additional","affiliation":[{"name":"From the Institute of Vascular Medicine, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L., Y.H.)"},{"name":"School of Biomedical Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L.,Y.H.), Chinese University of Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Yu","family":"Gong","sequence":"additional","affiliation":[{"name":"From the Institute of Vascular Medicine, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L., Y.H.)"},{"name":"School of Biomedical Sciences (W.S., C.-L.Z., L.G., L.H., Y.-Y.G., Q.D., L.Z., L.W., X.Y.T., J.-Y.L.,Y.H.), Chinese University of Hong 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