Sustained expression of thrombospondin-1 is associated with the development of glomerular and tubulointerstitial fibrosis in the remnant kidney model

Christian Hugo, Duk Hee Kang, Richard J. Johnson

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background/Aims: Transforming growth factor-β1(TGF-β1) has been implicated in the development of progressive nephrosclerosis in the remnant kidney model of chronic renal insufficiency. Thrombospondin-1 (TSP-1) is an extracellular matrix protein which has been recently shown to be capable of converting TGF-β from its latent to its active form. We studied the expression of TSP-1 mRNA and protein during the development of glomerular and tubulointerstitial nephrosclerosis in the renal ablation model particularly in relation to TGF-β1 expression. Methods: The remnant kidney model in the rat was investigated 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 7.5 weeks and 10 weeks after disease induction. Using single and double immunostaining techniques, renal tissues were examined for TSP-1 protein, TGF-β1, platelet-derived growth factor BB, extracellular matrix proteins, such as collagens and fibronectin, myofibroblast formation and macrophage influx. TSP-1 mRNA expression was investigated using a radioactive in situ hybridization technique. Results: De novo expression of TSP-1 mRNA and protein occurred in all glomerular cell types as well as in tubular cells, myofibroblasts and some macrophages in areas of tubulointerstitial injury. TSP-1 expression preceded and was sustained during the development of tubulointerstitial and glomerular fibrosis and was frequently localized at sites of increased expression of TGF-β1, but not of platelet-derived growth factor BB. Conclusion: In the remnant kidney model, the time course and localization of TSP-1 are consistent with its playing a role as a local activator of TGF-β1, thereby potentially participating in the development of nephrosclerosis.

Original languageEnglish
Pages (from-to)460-470
Number of pages11
JournalNephron
Volume90
Issue number4
DOIs
StatePublished - 2002

Keywords

  • Glomerulosclerosis
  • Remnant kidney model
  • TGF-β activation
  • Thrombospondin-1
  • Tubulointerstitial fibrosis

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