| http://purl.uniprot.org/citations/26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26565025 | http://www.w3.org/2000/01/rdf-schema#comment | "TGF-β is a pleiotropic cytokine that accumulates during kidney injuries, resulting in various renal diseases. We have reported previously that TGF-β1 induces the selective up-regulation of mitochondrial Nox4, playing critical roles in podocyte apoptosis. Here we investigated the regulatory mechanism of Nox4 up-regulation by mTORC1 activation on TGF-β1-induced apoptosis in immortalized podocytes. TGF-β1 treatment markedly increased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets p70S6K and 4EBP1. Blocking TGF-β receptor I with SB431542 completely blunted the phosphorylation of mTOR, p70S6K, and 4EBP1. Transient adenoviral overexpression of mTOR-WT and constitutively active mTORΔ augmented TGF-β1-treated Nox4 expression, reactive oxygen species (ROS) generation, and apoptosis, whereas mTOR kinase-dead suppressed the above changes. In addition, knockdown of mTOR mimicked the effect of mTOR-KD. Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-β1. Pharmacological inhibition of the MEK-ERK cascade, but not the PI3K-Akt-TSC2 pathway, abolished TGF-β1-induced mTOR activation. Inhibition of either ERK1/2 or mTORC1 did not reduce the TGF-β1-stimulated increase in Nox4 mRNA level but significantly inhibited total Nox4 expression, ROS generation, and apoptosis induced by TGF-β1. Moreover, double knockdown of Smad2 and 3 or only Smad4 completely suppressed TGF-β1-induced ERK1/2-mTORactivation. Our data suggest that TGF-β1 increases translation of Nox4 through the Smad-ERK1/2-mTORC1 axis, which is independent of transcriptional regulation. Activation of this pathway plays a crucial role in ROS generation and mitochondrial dysfunction, leading to podocyte apoptosis. Therefore, inhibition of the ERK1/2-mTORC1 pathway could be a potential therapeutic and preventive target in proteinuric and chronic kidney diseases."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.703116"xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Kim S.J."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Choi S.K."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Nguyen T.T."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Xu S."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Park K.S."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Das R."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Lee E.Y."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Quan X."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/author | "Cha S.K."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/pages | "30830-30842"xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/title | "Transforming Growth Factor beta1-induced Apoptosis in Podocytes via the Extracellular Signal-regulated Kinase-Mammalian Target of Rapamycin Complex 1-NADPH Oxidase 4 Axis."xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://purl.uniprot.org/core/volume | "290"xsd:string |
| http://purl.uniprot.org/citations/26565025 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26565025 |
| http://purl.uniprot.org/citations/26565025 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26565025 |
| http://purl.uniprot.org/uniprot/#_P63085-mappedCitation-26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26565025 |
| http://purl.uniprot.org/uniprot/#_B5AN18-mappedCitation-26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26565025 |
| http://purl.uniprot.org/uniprot/#_B2RSM1-mappedCitation-26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26565025 |
| http://purl.uniprot.org/uniprot/#_O35558-mappedCitation-26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26565025 |
| http://purl.uniprot.org/uniprot/#_P04202-mappedCitation-26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26565025 |
| http://purl.uniprot.org/uniprot/#_Q63844-mappedCitation-26565025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26565025 |