Structural and functional specificities of PDGF‐C and PDGF‐D, the novel members of the platelet‐derived growth factors family

Abstract

The platelet‐derived growth factor (PDGF) family was for more than 25 years assumed to consist of only PDGF‐A and ‐B. The discovery of the novel family members PDGF‐C and PDGF‐D triggered a search for novel activities and complementary fine tuning between the members of this family of growth factors. Since the expansion of the PDGF family, more than 60 publications on the novel PDGF‐C and PDGF‐D have been presented, highlighting similarities and differences to the classical PDGFs. In this paper we review the published data on the PDGF family covering structural (gene and protein) similarities and differences among all four family members, with special focus on PDGF‐C and PDGF‐D expression and functions. Little information on the protein structures of PDGF‐C and ‐D is currently available, but the PDGF‐C protein may be structurally more similar to VEGF‐A than to PDGF‐B. PDGF‐C contributes to normal development of the heart, ear, central nervous system (CNS), and kidney, while PDGF‐D is active in the development of the kidney, eye and brain. In adults, PDGF‐C is active in the kidney and the central nervous system. PDGF‐D also plays a role in the lung and in periodontal mineralization. PDGF‐C is expressed in Ewing family sarcoma and PDGF‐D is linked to lung, prostate and ovarian cancers. Both PDGF‐C and ‐D play a role in progressive renal disease, glioblastoma/medulloblastoma and fibrosis in several organs.

Platelet‐derived growth factor is involved in the differentiation of second heart field‐derived cardiac structures in chicken embryos

“…The role of PDGF-A and -C during development has been investigated in several nullmutant and overexpression mouse models. Phenotypical features of the PdgfcϪ/Ϫ mice largely overlap with those of PdgfaϪ/Ϫ mice, without a cardiac phenotype (Betsholtz, 2004;Ding et al, 2004;Reigstad et al, 2005). The hearts of the PdgfcϪ/Ϫ PdgfaϪ/Ϫ double mutants, however, showed lack of atrial septum formation (Ding et al, 2004;Reigstad et al, 2005).…”

“…In the heart, it induced strong proliferation of myocardial interstitial fibroblasts (Reigstad et al, 2005). Expansion of the cardiac interstitium in transgenic Pdgfc overexpression mice caused an altered myocardial architecture and an increased thickness of the ventricular walls (Ponten et al, 2003;Raines, 2004).…”

Growth factor delivery for oral and periodontal tissue engineering

“…These effects were shown to be time-and dose dependent [73]. The PDGF family is composed of four growth factors: PDGF-A, -B, and the most recently discovered PDGF-C and -D [74]. All of these participate in the wound-healing process, but, until now, only the three isoforms PDGF-AA, BB and AB were evaluated in periodontal therapy.…”

Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?

“…The PDGF family compromises four different members, PDGF-A, -B, -C, and -D, forming biological active homodimers (Betsholtz 2003). Lack or loss of PDGF-B leads to vascular dysfunction and vascular leakage (Gaengel et al 2009;Reigstad et al 2005;Tallquist and Kazlauskas 2004;Trojanowska 2008).…”