title: Blocking Mammalian Target of Rapamycin (mTOR) Attenuates HIF-1α Pathways Engaged-Vascular Endothelial Growth Factor (VEGF) in Diabetic Retinopathy.
abstract: OBJECTIVE
  Prior studies demonstrate that hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in development of diabetic retinopathy (DR). In this report, we particularly examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, namely vascular endothelial growth factor (VEGF).
  
  
  METHODS
  Streptozotocin (STZ) was systemically injected to induce hyperglycemia in rats. ELISA and Western Blot analysis were employed to determine the levels of HIF-1α and VEGF as well as expression of mTOR pathways in retinal tissues of control rats and STZ rats.
  
  
  RESULTS
  Our results show that HIF-1α and VEGF as well as VEGF receptor subtype 2 (VEGFR-2) were increased in STZ rats. Also, the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in diabetic retina compared with controls. Blocking mTOR by using rapamycin significantly attenuated activities of HIF-1α and VEGF signaling pathways.
  
  
  CONCLUSIONS
  Our data for the first time revealed specific signaling pathways engaged in the development of DR, including the activation of mTOR and HIF-1α -VEGF mechanism. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of DR often observed in clinics.
authors.affiliation: Department of Ophthalmology, General Hospital of Jinan Military Command, Jinan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Hongrui
authors.initials: H
authors.lastname: Gao
authors.forename: Guangjie
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013311:Streptozocin; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D040301:Vascular Endothelial Growth Factor Receptor-2; D058570:TOR Serine-Threonine Kinases; D053148:Caspase 3