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Vascular transcriptome landscape of Trail-/- mice: Implications and therapeutic strategies for diabetic vascular disease.
Cartland, Siân P; Lin, Ruby C Y; Genner, Scott; Patil, Manisha S; Martínez, Gonzalo J; Barraclough, Jennifer Y; Gloss, Brian; Misra, Ashish; Patel, Sanjay; Kavurma, Mary M.
Afiliação
  • Cartland SP; Heart Research Institute, Sydney, NSW, Australia.
  • Lin RCY; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • Genner S; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • Patil MS; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
  • Martínez GJ; Westmead Institute for Medical Research, Sydney, NSW, Australia.
  • Barraclough JY; Heart Research Institute, Sydney, NSW, Australia.
  • Gloss B; Heart Research Institute, Sydney, NSW, Australia.
  • Misra A; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • Patel S; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • Kavurma MM; Westmead Institute for Medical Research, Sydney, NSW, Australia.
FASEB J ; 34(7): 9547-9562, 2020 07.
Article em En | MEDLINE | ID: mdl-32501591
Circulating plasma TRAIL levels are suppressed in patients with cardiovascular and diabetic diseases. To identify novel targets in vascular metabolic diseases, genome-wide transcriptome of aortic tissue from Trail-/- versus Trail+/+ mice were interrogated. We found 861 genes differentially expressed with TRAIL deletion. Gene enrichment analyses showed many of these genes were related to inflammation, cell-to-cell cytoskeletal interactions, and transcriptional modulation. We identified vascular protective and pathological gene clusters, with Ifi205 as the most significantly reduced vascular protective gene, whereas Glut1, the most significantly increased pathological gene with TRAIL deletion. We hypothesized that therapeutic targets could be devised from such integrated analysis and validated our findings from vascular tissues of diabetic mice. From the differentially expressed gene targets, enriched transcription factor (TF) and microRNA binding motifs were identified. The top two TFs were Elk1 and Sp1, with enrichment to eight gene targets common to both. miR-520d-3p and miR-377-3p were the top enriched microRNAs with TRAIL deletion; with four overlapping genes enriched for both microRNAs. Our findings offer an alternate in silico approach for therapeutic target identification and present a deeper understanding of gene signatures and pathways altered with TRAIL suppression in the vasculature.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Perfilação da Expressão Gênica / Diabetes Mellitus Experimental / Angiopatias Diabéticas / Ligante Indutor de Apoptose Relacionado a TNF / Transcriptoma Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals / Humans Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica / Perfilação da Expressão Gênica / Diabetes Mellitus Experimental / Angiopatias Diabéticas / Ligante Indutor de Apoptose Relacionado a TNF / Transcriptoma Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals / Humans Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Austrália