| http://purl.uniprot.org/citations/23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23144758 | http://www.w3.org/2000/01/rdf-schema#comment | "Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression. Reactive oxygen species (ROS) have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated. In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs). Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, but did not change the serine phosphorylation of IRS-1. Nox4 gene silencing had a much greater inhibitory effect on insulin-induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP. Inhibition of Nox4 expression inhibited the transcriptional activity of VEGF through HIF-1. Overexpression of wild-type Nox4 was sufficient to increase VEGF transcriptional activity, and further enhanced insulin-stimulated the activation of VEGF. Downregulation of Nox4 expression decreased insulin-stimulated mRNA and protein expression of HIF-1α, but did not change the rate of HIF-1α degradation. Inhibition of Nox4 impaired insulin-stimulated VEGF expression, cell migration, cell proliferation, and tube formation in HMVECs. Our data indicate that Nox4-derived ROS are essential for HIF-1α-dependent VEGF expression, and angiogenesis in vitro induced by insulin. Nox4 may be an attractive therapeutic target for diabetic retinopathy caused by intensive insulin treatment."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0048393"xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Chen S."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Liu J."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Shi X."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Mei A."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Kang X."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Meng D."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/author | "Qian R."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/pages | "e48393"xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/title | "NADPH oxidase 4 mediates insulin-stimulated HIF-1alpha and VEGF expression, and angiogenesis in vitro."xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/23144758 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23144758 |
| http://purl.uniprot.org/citations/23144758 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23144758 |
| http://purl.uniprot.org/uniprot/Q9NPH5#attribution-849D996009B17D3DEEF0031CDEA1E2A0 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_D0VY79-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_A2A2V4-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_A0A0Y0IMM4-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_A0A0Y0J542-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_B2R617-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_B7Z523-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |
| http://purl.uniprot.org/uniprot/#_B7Z529-mappedCitation-23144758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23144758 |