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Title: Platelet-derived growth factor-D expression in developing and mature human kidneys
Authors: Changsirikulchai S.
Hudkins K.L.
Goodpaster T.A.
Volpone J.
Topouzis S.
Gilbertson D.G.
Alpers C.E.
Keywords: lymphokine
messenger RNA
PDGFD protein, human
platelet derived growth factor
platelet derived growth factor
platelet derived growth factor beta receptor
platelet derived growth factor D
unclassified drug
antibody specificity
gene expression regulation
molecular genetics
prenatal development
reverse transcription polymerase chain reaction
Western blotting
basolateral membrane
cell differentiation
cell interaction
controlled study
gene expression
glomerulus epithelium
human cell
human tissue
interstitial nephritis
kidney development
kidney epithelium
kidney homogenate
kidney interstitium
nucleotide sequence
priority journal
protein expression
protein family
protein function
protein localization
smooth muscle fiber
Antibody Specificity
Blotting, Western
Gene Expression Regulation, Developmental
Molecular Sequence Data
Platelet-Derived Growth Factor
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Issue Date: 2002
Abstract: Background. Platelet-derived growth factor (PDGF) is a family of growth regulatory molecules composed of sulfide-bonded dimeric structures. Two well-studied PDGF peptides (PDGF-A and PDGF-B) have been shown to mediate a wide range of biological effects. PDGF-D is a newly recognized member of the PDGF family. Initial studies of the PDGF-D gene found its expression in cells of the vascular wall, suggesting that it could participate in vascular development and pathology. However, its localization in human kidney tissues has never been studied. Methods. PDGF-D expression in fetal (N = 30) and adult (N = 25) human kidney tissues was examined by immunohistochemistry using an affinity-purified antibody raised to human PDGF-D. Antibody absorption with the immunizing peptide was employed to confirm the specificity of this antibody. PDGF-D protein and gene expression in human kidneys also were demonstrated by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Results. In the developing kidney, PDGF-D was first expressed by epithelial cells of comma- and S-shaped structures of the developing nephron, and most consistently in the visceral epithelial cells in the later stages of glomerular differentiation. In addition, PDGF-D could be found in mesenchymal, presumptively fibroblast cells in the interstitium of developing renal pelvis and in fetal smooth muscle cells in arterial vessels. In the adult normal kidney, PDGF-D was expressed by the visceral epithelial cells. There was persistent expression in arterial smooth muscle cells as well as in some neointimal smooth muscle cells of arteriosclerotic vessels, and expression in smooth muscle cells of vasa rectae in the medulla. PDGF-D could be identified at the basolateral membrane of some injured tubules in areas of chronic tubulointerstitial injury routinely encountered in aging kidneys. Western blotting of homogenates of adult kidneys demonstrated monospecific bands at 50 kD corresponding to previously established size parameter for this protein. RT-PCR of human kidney RNA resulted in a 918 basepair band, the sequence of which corresponded to human PDGF-D (Genbank number AF336376). Conclusions. To our knowledge, these are the first studies to localize PDGF-D in human kidneys and suggest that PDGF-D may have a role in kidney development. PDGF-D was shown to bind to PDGF β receptor, which localizes to mesangial cells, parietal epithelial cells, and interstitial fibroblasts, suggesting potential paracrine interactions between those cells and the visceral epithelium.
ISSN: 852538
Appears in Collections:SCOPUS 1983-2021

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