種田 積子
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Associate Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Obstructive uropathy in mice and humans: potential role for PDGF-D in the progression of tubulointerstitial injury.
Journal Formal name:Journal of the American Society of Nephrology : JASN
Abbreviation:J Am Soc Nephrol
ISSN code:(1046-6673)1046-6673(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 14(10),pp.2544-55
Author and coauthor Taneda Sekiko†, Hudkins Kelly L, Topouzis Stavros, Gilbertson Debra G, Ophascharoensuk Vuddhidej, Truong Luan, Johnson Richard J, Alpers Charles E
Publication date 2003/10
Summary 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 alpha (PDGF-Ralpha) and receptor beta (PDGF-Rbeta). Involvement of PDGF-B and PDGF-Rbeta 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-Ralpha and -Rbeta 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-Rbeta 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-Rbeta in both human obstructive nephropathy and the corresponding murine model of UUO.
PMID 14514732