PDGF-C Is a Proinflammatory Cytokine that Mediates Renal Interstitial Fibrosis

A New Look at Platelet-Derived Growth Factor in Renal Disease

“…109 Antagonism of PDGF-C using a neutralizing antiserum reduced the extent of renal tubulointerstitial fibrosis after unilateral ureter ligation. 110 These studies complement other studies in which cardiac overexpression of PDGF-C induced myocardial fibrosis. 111 Various interventions that reduce MC proliferation in vivo, such as administration of heparin, C-type natriuretic peptide, or antisense oligonucleotides against Egr-1, may act indirectly through inhibition of autostimulatory effects of endogenously produced PDGF.…”

The PDGFC CUB Domain Enhances Survival in PDGFC Mutant Mice

“…We did not observe premature death in pdgfc tm1lex mice up to 12 months of age and did not see sexdependent differences in viability on the C57BL/6 background, as has been reported for pdgfc tm1nagy mice [20]. Similar to Fredriksson L, et al [6] we observed a statistically significant decrease in body mass in C57BL/6 pdgfc tm1lex mice at 3 and 7 months (a 17 to 24% decrease, data not shown).…”

“…pdgfc tm1nagy mice have developmental abnormalities on a 129S1/Sv*129X/ SvJ background, specifically a lethal palate formation defect [5]. These mice are viable on a C57BL/6 background but have brain abnormalities [19,20]. Conversely, pdgfc tm1lex mice are viable in two backgrounds, C57BL/6 x 129S5/SvEvBrd and C57BL/6 though two alleles of pdgfrα are necessary for their viability.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Activation of either receptor chain mediates the transition from renal interstitial fibroblasts or pericytes to myofibroblasts (296). The respective ligands are either expressed by intrinsic renal cells (27,(297)(298)(299) (Figure 5) or are brought in by infiltrating leukocytes, in particular monocytes/macrophages, in the case of PDGF-C (298). Of particular relevance for renal fibrosis is the observation that PDGF-C knockout mice fail to develop renal interstitium (300), identifying it as a prominent mediator of renal interstitial changes.…”