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Relevance of periglomerular myofibroblasts in progression of human glomerulonephritis
1The Second Department of Internal Medicine, Faculty of Medicine, the University of Tokyo, Japan.
Abstract:
To clarify the pathological and clinical significance of periglomerular alpha-smooth muscle actin (alpha-SMA)-positive cells, we examined 51 needle-biopsy specimens from patients with human glomerulonephritis. Immunoelectron microscopy confirmed these cells were myofibroblasts showing characteristic features with abundant alpha-SMA-positive thin myofilaments. Nonsclerotic glomeruli with periglomerular myofibroblasts were larger in the Bowman's capsular planar area than nonsclerotic glomeruli without periglomerular myofibroblasts (24.7 +/- 6.0 x 10(3) microm2 v 19.9 +/- 8.5 x 10(3) microm2; P < 0.01). We studied the correlation between the clinical prognosis and the extent of periglomerular myofibroblasts in 24 patients with IgA nephropathy. Patients were divided into two groups; those with plasma creatinine levels within normal range at biopsy and significantly elevated at follow-up were designated group 1 (poor prognosis), and patients with plasma creatinine levels within normal range at biopsy and not significantly elevated at follow-up were designated group 2 (fair prognosis). In the kidneys of group 1 patients, periglomerular alpha-SMA was expressed more intensively than it was in the kidneys of group 2 patients (alpha-SMA expression score, 1.0 +/- 0.48 v 0.52 +/- 0.54; P < 0.05). These findings indicate that periglomerular myofibroblasts appeared surrounding the nonsclerotic hypertrophic glomeruli, which may lead finally to glomerulosclerosis. This report suggests that interaction between the glomerular cells and the periglomerular myofibroblasts may have a role in the progression of glomerular diseases.
Insights
Periglomerular myofibroblasts, identified by alpha-smooth muscle actin (alpha-SMA), are associated with larger glomeruli and poorer prognosis in glomerulonephritis patients. These cells may drive disease progression.
Area of Science:
- Nephrology
- Pathology
- Cell Biology
Background:
- Periglomerular cells expressing alpha-smooth muscle actin (alpha-SMA) are implicated in kidney disease.
- Their precise pathological and clinical significance in human glomerulonephritis remains unclear.
Purpose of the Study:
- To investigate the role of alpha-smooth muscle actin (alpha-SMA)-positive periglomerular cells in human glomerulonephritis.
- To determine the association between these cells and glomerular hypertrophy and clinical prognosis.
Main Methods:
- Analysis of 51 human glomerulonephritis needle-biopsy specimens.
- Immunoelectron microscopy to characterize alpha-SMA-positive cells.
- Correlation analysis between alpha-SMA expression, glomerular size, and clinical outcomes in IgA nephropathy patients.
Main Results:
- Alpha-SMA-positive cells were confirmed as myofibroblasts with characteristic ultrastructural features.
- Nonsclerotic glomeruli with periglomerular myofibroblasts were significantly larger than those without.
- Higher periglomerular alpha-SMA expression correlated with poorer renal function prognosis in IgA nephropathy.
Conclusions:
- Periglomerular myofibroblasts are associated with glomerular hypertrophy and may contribute to glomerulosclerosis.
- These cells play a role in the progression of glomerular diseases, suggesting potential therapeutic targets.