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Updated: Apr 1, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
DNA double-strand breaks induced intractable glomerular fibrosis in renal allografts
Yuki Matsui1, Yumi Sunatani2, Norifumi Hayashi1
1Department of Nephrology, School of Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
Backgrounds:
The relationship between DNA damage and glomerular fibrosis in renal allografts remains unclear.
Methods:
We examined renal allograft specimens from 35 patients in which DNA double-strand breaks (DSBs) and glomerular fibrosis were detected by phospho-histone H2A.X (γ-H2AX) expression and collagen (COL) types III, IV, and VI accumulation. We also examined the in vitro relationship between DNA damage and COL accumulation by mitomycin C (MMc)-induced DNA damage in human glomerular endothelial cells (HRGEc).
Results:
The γ-H2AX and COL type VI, which mainly accumulated in the subendothelial and mesangial regions, were positively correlated with the duration of the post-renal transplant (RT) period. In multiple regression analysis, the duration of the post-RT period and cg in the Banff '07 classification were identified as a significant predictor of COL type VI accumulation and γ-H2AX expression in the glomerular capillaries. In addition, the γ-H2AX-positive area was also identified as a predictor of glomerular accumulation of COL type VI. COL type VI was detected in the cytoplasm of the HRGEc, which was secreted into the supernatant after MMc stimulation with γ-H2AX expression. The number of γ-H2AX (-)/COL type VI (+) cells was inversely associated with the number of γ-H2AX (+)/COL type VI (-) cells during 24-h MMc treatment.
Conclusions:
Our findings suggest that the long-term RT induces DSBs and HRGEc-secreted COL type VI accumulation in the glomerular capillaries, which might progress to intractable glomerular fibrosis.
Insights
Long-term kidney transplants cause DNA damage and collagen VI buildup in glomerular capillaries, potentially leading to fibrosis. This study links DNA double-strand breaks (DSBs) to collagen VI accumulation in renal allografts.
Area of Science:
- Nephrology
- Molecular Biology
- Pathology
Background:
- The link between DNA damage and glomerular fibrosis in kidney transplants is not well understood.
- Investigating this relationship is crucial for understanding transplant outcomes.
Purpose of the Study:
- To explore the association between DNA double-strand breaks (DSBs) and glomerular fibrosis in renal allografts.
- To elucidate the role of human glomerular endothelial cells (HRGEc) in collagen accumulation following DNA damage.
Main Methods:
- Analysis of renal allograft specimens (n=35) for DSBs (γ-H2AX) and collagen types III, IV, VI.
- In vitro study using mitomycin C (MMc) to induce DNA damage in HRGEc and assess collagen secretion.
Main Results:
- γ-H2AX and collagen type VI accumulation correlated positively with post-transplant duration.
- Post-transplant duration and Banff classification (cg) predicted collagen VI and γ-H2AX.
- MMc-induced DNA damage in HRGEc led to γ-H2AX expression and collagen type VI secretion.
Conclusions:
- Long-term renal transplantation induces DSBs and collagen type VI accumulation in glomerular capillaries.
- HRGEc-secreted collagen type VI may contribute to the progression of glomerular fibrosis.
- Findings suggest a mechanism linking DNA damage to fibrosis in renal allografts.
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