Document Detail


Platelet-derived growth factor-D expression in developing and mature human kidneys.
MedLine Citation:
PMID:  12427128     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 beta receptor, which localizes to mesangial cells, parietal epithelial cells, and interstitial fibroblasts, suggesting potential paracrine interactions between those cells and the visceral epithelium.
Authors:
Siribha Changsirikulchai; Kelly L Hudkins; Tracy A Goodpaster; John Volpone; Stavros Topouzis; Debra G Gilbertson; Charles E Alpers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Kidney international     Volume:  62     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-12     Completed Date:  2003-05-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2043-54     Citation Subset:  IM    
Affiliation:
Department of Medicine, Srinakharinwirot University, Bangkok, Thailand.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF336376
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibody Specificity
Blotting, Western
Fetus / chemistry
Gene Expression Regulation, Developmental
Humans
Immunohistochemistry
Kidney / chemistry*,  embryology*,  physiology
Lymphokines*
Molecular Sequence Data
Platelet-Derived Growth Factor / analysis*,  genetics,  immunology
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
DK47959/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Lymphokines; 0/PDGFD protein, human; 0/Platelet-Derived Growth Factor; 0/RNA, Messenger

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