Obstructive uropathy in mice and humans: Potential role for PDGF-D in the progression of tubulointerstitial injury

Sekiko Taneda, Kelly L. Hudkins, Stavros Topouzis, Debra G. Gilbertson, Vuddhidej Ophascharoensuk, Luan Truong, Richard J. Johnson, Charles E. Alpers

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Tubulointerstitial fibrosis is a major characteristic of progressive renal diseases. Platelet-derived growth factor (PDGF) is a family of growth regulatory molecules consisting of PDGF-A and -B, along with the newly discovered PDGF-C and -D. They signal through cell membrane receptors, PDGF receptor α (PDGF-Rα) and receptor β (PDGF-β). Involvement of PDGF-B and PDGF-Rβ in the initiation and progression of renal fibrosis has been well documented. The authors studied the localization of PDGF ligands and receptors by immunohistochemistry, with emphasis on the role of PDGF-D in murine renal fibrosis induced by unilateral ureteral obstruction (UUO). In mice with UUO, de novo expression of PDGF-D was detected in interstitial cells at day 4, which increased to maximal expression at day 14. Increased expression of PDGF-B by interstitial cells and in some tubules was observed after day 4. The diseased mice did not show augmentation of PDGF-A or PDGF-C proteins in the areas of fibrosis. PDGF-Rα and -Rβ protein expression was increased in interstitial cells after day 4 and reached maximal expression at day 14. Human renal nephrectomies (n = 10) of chronic obstructive nephropathy demonstrated similar de novo expression of PDGF-D in interstitial cells, correlating with expression of PDGF-Rβ and PDGF-B, as it did in the murine model. These observations suggest that PDGF-D plays an important role in the pathogenesis of tubulointerstitial injury through binding of PDGF-Rβ in both human obstructive nephropathy and the corresponding murine model of UUO.

Original languageEnglish (US)
Pages (from-to)2544-2555
Number of pages12
JournalJournal of the American Society of Nephrology
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2003

ASJC Scopus subject areas

  • Nephrology

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