title: All-Trans Retinoic Acid Attenuates Hypoxia-Induced Injury in NRK52E Cells via Inhibiting NF-x03BA;B/VEGF and TGF-β2/VEGF Pathway.
abstract: OBJECTIVE
  Hypoxia has recently been proposed as one of the most important factors in progressive renal injury. Hypoxia-induced vascular endothelial growth factor (VEGF) expression may play a critical role in maintaining peritubular capillary endothelium in renal disease. This study was designed to investigate the effect and underlying mechanism of all-trans retinoic acid (ATRA) on hypoxia-induced injury in NRK52E cells.
  
  
  METHODS
  For mimicking hypoxia, cells were treated with 100 µM of cobalt chloride (CoCl2). The cell viability, expression of VEGF, p65, transforming growth factor-β2 (TGF-β2) and serine carboxypeptidase 1 (Scpep1), and nuclear factor of kappaB (NF-x03BA;B) activities after ATRA treatment were determined by MTT, western blot and electrophoretic mobility shift assay. Co-immunoprecipitation analysis was performed to demonstrate whether Scpep1 interacted with TGF-β2.
  
  
  RESULTS
  It was found that CoCl2 triggered hypoxia injury and significantly reduced cell viability. ATRA pretreatment increased the cell survival rate. Under hypoxic conditions, the expression of VEGF, p65 and TGF-β2 increased. Addition of ATRA significantly attenuated the expression of VEGF, p65 and TGF-β2. There was a corresponding variation of NF-x03BA;B/DNA binding activities. In addition, ATRA stimulated Scpep1 expression under normoxic and hypoxia condition. Furthermore, TGF-β2 interacted with Scpep1.
  
  
  CONCLUSIONS
  This study indicated that ATRA may attenuate hypoxia-induced injury in NRK52E cells via inhibiting NF-x03BA;B/VEGF and TGF-β2/VEGF pathway.
authors.affiliation: Department of Nephrology, Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second Hospital, Huai'an, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Ai-Mei
authors.initials: AM
authors.lastname: Gao
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Ji
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhong
authors.forename: Hai-Lun
authors.initials: HL
authors.lastname: Li
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D043402:Cathepsin A / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D047468:Immunoprecipitation; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D051996:Transcription Factor RelA; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D003035:Cobalt; D014212:Tretinoin; D043402:Cathepsin A; C018021:cobaltous chloride