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[Expression of FGF2, FGF receptor-1 and alpha-smooth muscle actin in experimental mesangial proliferative nephritis]
1Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
Abstract:
Mesangial cell (MC) proliferation is the principal cause of glomerulonephritis and glomerulosclerosis. Previous studies have demonstrated that various cytokines and growth factors are MC mitogens. In vitro, basic fibroblast growth factor (FGF2) stimulates MC proliferation. In the present study, two series of experiments were conducted using rats with anti-Thy 1.1 mesangial proliferative glomerulonephritis. The first series of experiments was designed to clarify the expression relationship between FGF2, FGF, receptor-1 (FGFR1) and alpha-smooth muscle actin (alpha-SMA). The second series examined the effect of intravenous administration of recombinant FGF2 in this model. The first series involving in situ hybridization with FGF2 and FGFR1 cRNA probes, showed that these mRNAs were expressed in the mesangial areas during the proliferative phase (days 4-7). Simultaneously, the alpha SMA scores of glomeruli also increased. In the second series, FGF2 was administered at 6, 12 and 24 hours (early group) and at 4, 5, and 6 days (late group) after disease induction. On day 7, there were more glomerular cells positive for proliferative cell nuclear antigen (PCNA) in the late group than in the control and early groups and the alpha-SMA scores of the glomeruli had increased in the late group. On day 14, the number of mesangial cells mainly increased in the late group. These findings suggest that FGF2 and FGFR1 showed significant correlation with the phenotypic changes of MC.
Insights
Basic fibroblast growth factor (FGF2) and its receptor (FGFR1) are linked to mesangial cell proliferation in glomerulonephritis. Targeting FGF2 may offer new therapeutic strategies for kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Context:
- Mesangial cell (MC) proliferation drives glomerulonephritis and glomerulosclerosis.
- Cytokines and growth factors, including basic fibroblast growth factor (FGF2), are known MC mitogens.
- In vitro studies confirm FGF2 stimulates MC proliferation.
Purpose:
- To investigate the expression relationship between FGF2, FGF receptor-1 (FGFR1), and alpha-smooth muscle actin (alpha-SMA) in a rat model of anti-Thy 1.1 mesangial proliferative glomerulonephritis.
- To examine the therapeutic effect of intravenous recombinant FGF2 administration on this glomerulonephritis model.
Summary:
- In situ hybridization revealed FGF2 and FGFR1 mRNA expression in mesangial areas during the proliferative phase (days 4-7), coinciding with increased alpha-SMA scores.
- Intravenous FGF2 administration, particularly in the late phase (days 4-6 post-induction), significantly increased glomerular cells positive for proliferative cell nuclear antigen (PCNA) on day 7.
- Late-phase FGF2 treatment also led to increased alpha-SMA scores and mesangial cell numbers by day 14, suggesting a correlation between FGF2/FGFR1 and MC phenotypic changes.
Impact:
- These findings highlight a significant correlation between FGF2, FGFR1, and the phenotypic alterations of mesangial cells in glomerulonephritis.
- The study suggests that FGF2 plays a crucial role in the proliferative phase of mesangial proliferative glomerulonephritis.
- This research provides a basis for exploring FGF2-targeted therapies for kidney diseases characterized by mesangial cell proliferation.