title: [Effects of TIMP-1 on PTEN expression on renal tubular epithelial cells].
abstract: OBJECTIVE
  To investigate the role of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in regulating both angiogenesis and the expressions of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and vascular endothelial growth factor (VEGF)/Flk-1 expression in human proximal tubular epithelial cells (HKC).
  
  
  METHODS
  HKC cells were transfected with two recombinant plasmids containing sense and antisense full-length TIMP-1 cDNA (TIMP-1S-pcDNA3.0 and TIMP-1AS-pcDNA3.0, respectively) constructed previously, or treated with 100 µmol/L MMP-2/MMP-9 inhibitor III (with similar cellular enzyme suppression activity with sense TIMP-1 plasmid). The mRNA expression of TIMP-1, MMP-2, MMP-9, PTEN, VEGF and Flk-1 were examined by RT-PCR. In each group, the expression of PTEN, VEGF and Flk-1 were also detected using an indirect immunofluorescence assay.
  
  
  RESULTS
  Compared with non-transfected cells and cells transfected with the empty vector, sense TIMP-1-transfected cells showed obviously upregulated PTEN expression (P<0.05) and significantly lowered gelatinase activity (P<0.05) and VEGF and Flk-1 expressions (P<0.05). Transfection with the antisense TIMP-1 plasmid produced the reverse results (P<0.05). MMP-2/MMP-9 inhibitor III did not obviously affected the expression of PTEN, VEGF or Flk-1 as compared with the non-transfected or empty vector-transfected cells.
  
  
  CONCLUSIONS
  In the aging progress, the renal tissues express high levels of TIMP-1 to upregulate PTEN expression via a MMP-independent pathway, and subsequently down-regulates the expression of VEGF and Flk-1 to cause aging-related impairment of renal angiogenesis. These findings provide new evidence for understanding the role of TIMP-1 in renal aging.
authors.affiliation: Department of Nephrology, Second Xiangya Hospital of Central South University, Changsha, China. 798242742@qq.com
authors.forename: Junxiang
authors.initials: J
authors.lastname: Chen
authors.forename: Guangyan
authors.initials: G
authors.lastname: Cai
authors.forename: Li
authors.initials: L
authors.lastname: Zhuo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.forename: Suozhu
authors.initials: S
authors.lastname: Shi
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology; D061965:Matrix Metalloproteinase Inhibitors; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human