Over-expression of platelet-derived growth factor in human diabetic nephropathy.
BACKGROUND
The pathogenetic mechanisms responsible for progressive renal impairment of diabetic nephropathy are still poorly understood, despite its growing incidence. Increasing evidence suggests that growth factors may contribute to the initiation and progressive fibrosis of diabetic nephropathy. In this study, the gene expression and protein distribution of platelet-derived growth factor-A and -B (PDGF-A and PDGF-B) in human diabetic nephropathy were examined.


METHODS
PDGF-A and PDGF-B mRNA levels in surplus renal biopsy tissue from seven patients with overt diabetic nephropathy and six nephrectomy samples were examined using quantitative reverse transcription-polymerase chain reaction (RT-PCR). In addition, each sample was also examined immunohistochemically to quantify and localize peptide expression of each PDGF isoform.


RESULTS
Gene expression of PDGF-A and PDGF-B mRNA were increased 22- and 6-fold, respectively, in biopsies from patients with diabetic nephropathy compared with control tissue. Immunostaining also demonstrated increased peptide expression of both PDGF-A and PDGF-B in diabetic nephropathy, with each isoform showing a specific pattern of tissue distribution.


CONCLUSIONS
The findings of increased gene and protein expression of PDGF in renal biopsies from patients with diabetic nephropathy imply a potential role for this prosclerotic growth factor in the development of the progressive fibrosis that characterizes human diabetic kidney disease.
Langham
Robyn G
RG
University of Melbourne St Vincent's Hospital Department of Medicine, Fitzroy, Australia. rlangham@medstv.unimelb.edu.au
Kelly
Darren J
DJ
Maguire
Julie
J
Dowling
John P
JP
Gilbert
Richard E
RE
Thomson
Napier M
NM
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000235:genetics*; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000032:analysis* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A