title: Smad7 gene transfer attenuates angiogenesis in peritoneal dialysis rats.
abstract: OBJECTIVE
  Transforming growth factor-β (TGF-β) has been shown to play a role in peritoneal angiogenesis associated with peritoneal dialysis (PD). The present study investigated whether blockade of TGF-β signalling with Smad7 has a therapeutic effect on PD induced-peritoneal angiogenesis.
  
  
  METHODS
  A rat model of peritoneal dialysis was induced by a daily intraperitoneal injection of 4.25% Dianeal and lipopolysaccharides. PD rats were transfected with a doxycycline regulated, Smad7-expressing plasmid using an ultrasound-microbubble-mediated system on day 0 and day 14 after initiation of PD and an empty vector was used as control. Peritoneal microvessel density (MVD) in peritoneal tissue was assessed by anti-CD31 immunohistochemistry after 4 weeks of PD and peritoneal angiogenic growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) was also examined by immunofluorescence, western blot and reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  In contrast to the normal control group, at 4 weeks after PD, PD rats displayed peritoneal lesions, peritoneal angiogenesis and increased mRNA and protein expression of VEGF, bFGF and PDGF. Smad7 gene transfer significantly attenuated the peritoneal MVD and inhibited the upregulation of VEGF, bFGF and PDGF. Moreover, inhibition of peritoneal angiogenesis by overexpression of Smad7 was associated with inhibition of phosphorylation of Smad3 and downregulation of TGF-β expression.
  
  
  CONCLUSIONS
  Smad7 gene transfer via an ultrasound-microbubble-mediated system is able to attenuate peritoneal angiogenesis in a rat model of PD. Those results suggest that blockade of the TGF-β/Smad signalling pathway may represent a novel therapeutic approach to prevent PD-induced peritoneal angiogenesis.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Peng
authors.forename: Xianrui
authors.initials: X
authors.lastname: Dou
authors.forename: Wenke
authors.initials: W
authors.lastname: Hao
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Lan
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010529:Peritoneal Cavity / Q000098:blood supply*; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010743:Phospholipids / Q000008:administration & dosage; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000096:biosynthesis* / Q000235:genetics; D013459:Sulfur Hexafluoride / Q000008:administration & dosage; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D010743:Phospholipids; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C420843:contrast agent BR1; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; D013459:Sulfur Hexafluoride