Role of platelet-derived growth factor-CC in capillary rarefaction in renal fibrosis

Am J Pathol. 2015 Aug;185(8):2132-42. doi: 10.1016/j.ajpath.2015.04.022.


We have identified platelet-derived growth factor (PDGF)-CC as a potent profibrotic mediator in kidney fibrosis and pro-angiogenic mediator in glomeruli. Because renal fibrosis is associated with progressive capillary rarefaction, we asked whether PDGF-CC neutralization in fibrosis might have detrimental anti-angiogenic effects leading to aggravated peritubular capillary loss. We analyzed capillary rarefaction in mice with and without PDGF-CC neutralization (using genetically deficient mice and neutralizing antibodies), in three different models of renal interstitial fibrosis, unilateral ureteral obstruction, unilateral ischemia-reperfusion, Col4a3-deficient (Alport) mice, and healthy animals. Independent of the effect of PDGF-CC neutralization on renal fibrosis, we found no difference in capillary rarefaction between PDGF-CC-neutralized mice and mice with intact PDGF-CC. We also found no differences in microvascular leakage (determined by extravasation of Evans Blue Dye) and in renal relative blood volume quantified using in vivo microcomputed tomography. PDGF-CC neutralization had no effects on renal microvasculature in healthy animals. Capillary endothelium did not express PDGF receptor-α, suggesting that potential PDGF-CC effects would have to be indirect. PDGF-CC neutralization or deficiency was not associated with preservation or accelerated loss of peritubular capillaries, suggesting no significant pro-angiogenic effects of PDGF-CC during renal fibrosis. From a clinical perspective, the profibrotic effects of PDGF-CC outweigh the pro-angiogenic effects and, thus, do not limit a potential therapeutic use of PDGF-CC inhibition in renal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / metabolism*
  • Capillaries / pathology
  • Disease Models, Animal
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Mice
  • Mice, Knockout
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism*
  • Ureteral Obstruction / metabolism
  • Ureteral Obstruction / pathology


  • Lymphokines
  • Platelet-Derived Growth Factor
  • platelet-derived growth factor C