title: Thrombospondin-1 short hairpin RNA suppresses tubulointerstitial fibrosis in the kidney of ureteral obstruction by ameliorating peritubular capillary injury.
abstract: OBJECTIVE
  Thrombospondin-1 (TSP-1), a naturally occurring inhibitor of angiogenesis, is an important mediator of renal fibrosis in clinical and experimental kidney disease. Increasing evidence shows that the microvasculature plays a critical role in progressive renal disease. The present study was undertaken to investigate whether interstitial fibrosis could be prevented by abolishing TSP-1 function in unilateral ureteral obstruction (UUO)-induced renal fibrosis.
  
  
  RESULTS
  A short hairpin RNA vector, designated Thbs-1, significantly suppressed TSP-1 in both transcriptional and translational levels in in vitro-cultured cells and in vivo fibrosis-induced mouse kidney. Furthermore, TSP-1 RNA interference increased the protein level of vascular endothelial growth factor (VEGF) and the density of peritubular capillaries (PTCs), reduced the expression of hypoxia-inducible factor-1α in tubulointerstitial cells, and collagen III and the connective tissue growth factor expression were markedly reduced from day 7 after UUO-induced fibrosis, but un- or vector-treated mice maintained their expression. TSP-1 shRNA suppressed the protein level of TSP-1, increased VEGF expression and PTC density and alleviated the development of renal interstitial fibrosis in UUO mice.
  
  
  CONCLUSIONS
  These data suggest that inhibition of TSP-1 expression prevented tubulointerstitial fibrosis through ameliorating PTC injury.
authors.affiliation: Department of Nephrology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, PR China. sdxyfy@yahoo.cn
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ma
authors.forename: Hong
authors.initials: H
authors.lastname: Han
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Yin
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.forename: Jinhong
authors.initials: J
authors.lastname: Feng
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.forename: Aiguo
authors.initials: A
authors.lastname: Xiao
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology* / Q000502:physiology; D002478:Cells, Cultured; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009395:Nephritis, Interstitial / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D014517:Ureteral Obstruction / Q000235:genetics / Q000473:pathology / Q000628:therapy*
chemical_list: D034741:RNA, Small Interfering; D019700:Thrombospondin 1