| http://purl.uniprot.org/citations/30816805 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30816805 | http://www.w3.org/2000/01/rdf-schema#comment | "Objective-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 db/db mice and the molecular mechanisms involved. Approach and Results-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 db/db mouse aortas, suggesting a decreased TFEB activity. Adenoviral TFEB overexpression reduces endothelial inflammation as evidenced by decreased expression of vascular inflammatory markers in db/db 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-κB (nuclear factor-kappa B) signaling. Indeed, luciferase assay shows TFEB suppresses NF-κB transcriptional activity. Mechanistically, TFEB suppresses IKK (IκB kinase) activity to protect IκB-α 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 (Krüppel-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. Conclusions-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 IκBα level to suppress NF-κB activity. KLF2 mediates TFEB upregulation in response to laminar flow."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.org/dc/terms/identifier | "doi:10.1161/atvbaha.119.312316"xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Huang Y."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Qu D."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Song W."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Zhao L."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Zhang C.L."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "He L."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Jin N."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Chan T.F."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Gou L."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Gong Y.Y."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Tian X.Y."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/author | "Luo J.Y."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/name | "Arterioscler Thromb Vasc Biol"xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/pages | "719-730"xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/title | "Endothelial TFEB (Transcription Factor EB) Restrains IKK (IkappaB Kinase)-p65 Pathway to Attenuate Vascular Inflammation in Diabetic db/db Mice."xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://purl.uniprot.org/core/volume | "39"xsd:string |
| http://purl.uniprot.org/citations/30816805 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30816805 |
| http://purl.uniprot.org/citations/30816805 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30816805 |
| http://purl.uniprot.org/uniprot/#_D0FZQ3-mappedCitation-30816805 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30816805 |
| http://purl.uniprot.org/uniprot/#_D3Z782-mappedCitation-30816805 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30816805 |