Over-expression of platelet-derived growth factor in human diabetic nephropathy

Nephrol Dial Transplant. 2003 Jul;18(7):1392-6. doi: 10.1093/ndt/gfg177.

Abstract

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.

MeSH terms

  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology*
  • Gene Expression / genetics*
  • Humans
  • Kidney / chemistry
  • Kidney / pathology
  • Platelet-Derived Growth Factor / analysis*
  • Platelet-Derived Growth Factor / genetics*
  • Protein Isoforms / analysis
  • Protein Isoforms / genetics
  • Proto-Oncogene Proteins c-sis / analysis*
  • Proto-Oncogene Proteins c-sis / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Platelet-Derived Growth Factor
  • Protein Isoforms
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • platelet-derived growth factor A