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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis
M Matsuda1, K Shikata, H Makino
1Third Department of Internal Medicine, Okayama University Medical School, Japan.
Insights
Platelet-derived growth factor (PDGF) drives mesangial proliferative glomerulonephritis. Increased PDGF-B and PDGFR-beta expression correlates with glomerular injury and crescent formation, suggesting PDGF
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Platelet-derived growth factor (PDGF) is a key mitogen for diverse cell types.
- Its role in human glomerulonephritis pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the gene and protein expression of PDGF-B and its receptor, PDGFR-beta, in human glomerulonephritis.
- To correlate PDGF pathway activation with glomerular injury and disease progression.
Main Methods:
- Utilized nonradioactive in situ hybridization and immunohistochemical techniques.
- Analyzed renal biopsy specimens from patients with various glomerulonephritis forms and healthy controls.
- Quantified mRNA and protein expression of PDGF-B and PDGFR-beta.
Main Results:
- Significantly elevated PDGF-B and PDGFR-beta mRNA expression observed in mesangial proliferative glomerulonephritis glomeruli.
- Increased protein expression of PDGF-B and PDGFR-beta correlated with elevated mRNA levels.
- Glomerular injury severity positively correlated with PDGF and PDGFR mRNA-positive cell counts.
- PDGF-B and PDGFR-beta expression found on capillary walls, cellular crescents, and interstitial cells.
Conclusions:
- PDGF acts as a significant mediator in the development of human mesangial proliferative glomerulonephritis.
- PDGF signaling pathways are implicated in crescent formation and tubulo-interstitial injury.
- Targeting PDGF may offer therapeutic potential for glomerulonephritis treatment.
Abstract:
Platelet-derived growth factor (PDGF) is an important mitogenic factor for various cells. In order to elucidate the role of PDGF in the development of human glomerulonephritis, we examined the gene and protein expression of the PDGF-B chain (PDGF-B) and PDGF-beta receptor (PDGFR-beta) in renal biopsy specimens from patients with various forms of glomerulonephritis using a nonradioactive in situ hybridization and an immunohistochemical technique. The mRNA expression of PDGF-B and PDGFR-beta was significantly increased in the glomeruli of patients with mesangial proliferative glomerulonephritis (IgA nephropathy, Henoch-Schönlein purpura nephritis, and lupus nephritis) compared with those in normal glomeruli. In cases with increased protein expression of PDGF-B and PDGFR-beta, each mRNA expression was also increased. The degree of glomerular injury was positively correlated with the number of mRNA-positive cells for both PDGF and PDGF receptor. There was also a positive correlation between the number of mRNA-positive cells for PDGF-B and PDGFR-beta. PDGF-B and PDGFR-beta were also expressed on cells of the capillary wall, cellular crescents and infiltrated cells in the interstitium. The results suggest that PDGF acts as an important and common mediator for the development of various forms of human mesangial proliferative glomerulonephritis. Furthermore, PDGF may participate in crescent formation and tubulo-interstitial injury.
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