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|dc.description.abstract||Chronic allograft nephropathy (CAN), a descriptive term denoting chronic scarring injury of the renal parenchyma and vasculature in allograft kidneys arising from various etiologies including chronic rejection, is the most common cause of late allograft failure, but mediators of this progressive injury largely remain unknown. We hypothesized that platelet-derived growth factor D (PDGF-D) and its specific receptor PDGF-Rβ may be an important mediator in the pathogenesis of CAN and, hence, sought to identify its expression in this setting. Allograft nephrectomies demonstrating CAN, obtained from patients with irreversible transplant kidney failure (n = 15), were compared with renal tissues without prominent histopathological abnormalities (n = 18) and a series of renal allograft biopsies demonstrating acute vascular rejection (AVR) (n = 12). Antibodies to PDGF-D and PDGF-Rβ were used for immunohistochemistry. Double and triple immunohistochemistry was used to identify cell types expressing PDGF-D. PDGF-D was widely expressed in most neointimas in arteries exhibiting the chronic arteriopathy of CAN and only weakly expressed in a small proportion of sclerotic arteries in the other 2 groups. Double and triple immunolabeling demonstrated that the neointimal cells expressing PDGF-D were α-smooth muscle actin-expressing cells, but not infiltrating macrophages or endothelial cells. PDGF-Rβ expression evaluated in serial sections was localized to the same sites where neointimal PDGF-D was expressed. PDGF-Rβ was expressed in interstitial cells more abundantly in the CAN group compared with the normal and AVR groups, without demonstrable colocalization of PDGF-D. PDGF-D is present in the neointima of the arteriopathy of CAN, where it can engage PDGF-Rβ to promote mesenchymal cell migration, proliferation, and neointima formation. PDGF-D may engage the PDGF-Rβ to promote interstitial injury in chronic allograft injury, but its sources within the interstitium were unidentified. © 2008 Elsevier Inc. All rights reserved.|
|dc.subject||platelet derived growth factor beta receptor|
|dc.subject||platelet derived growth factor D|
|dc.subject||chronic allograft nephropathy|
|dc.subject||Muscle, Smooth, Vascular|
|dc.subject||Platelet-Derived Growth Factor|
|dc.subject||Receptor, Platelet-Derived Growth Factor beta|
|dc.title||Identification of platelet-derived growth factor D in human chronic allograft nephropathy|
|dc.identifier.bibliograpycitation||Human Pathology. Vol 39, No.3 (2008), p.393-402|
|Appears in Collections:||Scopus 1983-2021|
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