Obstructive Uropathy in Mice and Humans: Potential Role for PDGF-D in the Progression of Tubulointerstitial Injury

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 (PDGF-R) and receptor (PDGF-R). Involve- ment of PDGF-B and PDGF-R in the initiation and progres- sion 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 obstruc- tion (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 expres- sion of PDGF-B by interstitial cells and in some tubules was observed after day 4. The diseased mice did not show augmen- tation of PDGF-A or PDGF-C proteins in the areas of fibrosis. PDGF-R and -R protein expression was increased in inter- stitial cells after day 4 and reached maximal expression at day 14. Human renal nephrectomies (n 10) of chronic obstruc- tive nephropathy demonstrated similar de novo expression of PDGF-D in interstitial cells, correlating with expression of PDGF-R 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-R in both human obstructive nephropathy and the corresponding murine model of UUO.