title: Neutrophil gelatinase-associated lipocalin protects renal tubular epithelial cells in hypoxia-reperfusion by reducing apoptosis.
abstract: OBJECTIVE
  The aim of this study was to elucidate the role of neutrophil gelatinase-associated lipocalin (NGAL) in regulating apoptosis of tubular epithelial cells in a hypoxia-reperfusion model.
  
  
  METHODS
  A hypoxia-reperfusion model was established with NRK-52E cells to assess apoptosis and cell cycle progression after the addition of NGAL. We investigated the expression of four apoptosis factors, Bcl-2, Bax, Fas and FasL, as well as the expression level of two NGAL receptors, 24p3R and megalin, by both Western blot and real-time PCR.
  
  
  RESULTS
  NGAL induced cell proliferation and reduced apoptosis by regulating four apoptosis factors Bcl-2, Bax, Fas and FasL. Western blot demonstrated that the two NGAL receptors, 24p3R and megalin, were increased after hypoxia-reperfusion, which was reduced by exogenous NGAL. Moreover, overexpression of the two receptors induced the expression of the anti-apoptotic factor Bcl-2 and reduced the expression of pro-apoptotic Bax, Fas and FasL.
  
  
  CONCLUSIONS
  These findings indicate that NGAL reduces apoptosis by regulating the four apoptosis factors Bcl-2, Bax, Fas and FasL through its two receptors 24p3R and megalin. These results also suggest that ectopic expression of NGAL in renal cells might provide a therapeutic strategy in ischemia-reperfusion by reducing apoptosis and promoting renal cell proliferation.
authors: Department of Nephrology, Songjiang Hospital Affiliated to the First People´s Hospital of Shanghai Jiaotong University, 746 Songjiang Zhongshan Road, Shanghai, 201600, China, zangxiujuan@163.com.
authors: Xiujuan
authors: X
authors: Zang
authors: Feng
authors: F
authors: Zheng
authors: Hai-juan
authors: HJ
authors: Hong
authors: Yan
authors: Y
authors: Jiang
authors: Ying
authors: Y
authors: Song
authors: Yanping
authors: Y
authors: Xia
mesh_terms: D000209:Acute-Phase Proteins / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules; D000071068:Lipocalin-2; D054834:Lipocalins / Q000494:pharmacology*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C000597369:24p3R receptor, rat; D000209:Acute-Phase Proteins; C494828:Bax protein, rat; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051028:bcl-2-Associated X Protein; D019014:fas Receptor