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Growth factor gene expression in kidney of murine polycystic kidney disease
T Nakamura1, I Ebihara, I Nagaoka
1Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Abstract:
The DBA/2FG-pcy mouse has a form of slowly progressive kidney disease that appears similar in many respects to that seen in the autosomal dominant form of human polycystic kidney disease. The aim of this study was to examine the mRNA expression of growth-related proteins in kidney obtained from DBA/2FG-pcy mice and control DBA/2 mice at 8, 16, and 30 wk of age. The mRNA levels encoding for proliferating cell nuclear antigen (PCNA), transforming growth factor (TGF)-beta, platelet-derived growth factor (PDGF)-A and PDGF-B chains, insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) were increased with the progression of cystic lesions in the kidneys of DBA/2FG-pcy mice. At 30 wk of age, mRNA levels of PCNA, TGF-beta, PDGF-A and PDGF-B chains, IGF-I, and bFGF were increased 5.4-fold, 4.8-fold, 4.4-fold, 3.8-fold, 3.7-fold, and 4.6-fold, respectively, compared with those of control DBA/2 mice. In contrast, mRNA levels for epidermal growth factor in kidney of DBA/2FG-pcy mice decreased with age as compared with those of DBA/2 mice. These results suggest that decreased epidermal growth factor mRNA expression and increased expression of PCNA, TGF-beta, PDGF-A and PDGF-B chains, IGF-I, and bFGF mRNA may contribute to the progression of cystic lesions in DBA/2FG-pcy mice.
Insights
Kidney disease in DBA/2FG-pcy mice shows increased growth-related gene expression, including proliferating cell nuclear antigen (PCNA) and transforming growth factor-beta (TGF-beta). These changes may drive the progression of polycystic kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- The DBA/2FG-pcy mouse model exhibits a slowly progressive kidney disease.
- This condition shares similarities with human autosomal dominant polycystic kidney disease (ADPKD).
Purpose of the Study:
- To investigate the mRNA expression of key growth-related proteins in the kidneys of DBA/2FG-pcy mice.
- To compare gene expression patterns between affected mice and control DBA/2 mice at different ages (8, 16, and 30 weeks).
Main Methods:
- Quantitative analysis of mRNA levels using techniques such as RT-PCR or similar methods.
- Comparison of gene expression profiles in kidney tissues from DBA/2FG-pcy and DBA/2 mice at specified time points.
Main Results:
- Elevated mRNA expression of proliferating cell nuclear antigen (PCNA), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF)-A and -B chains, insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) was observed.
- At 30 weeks, these genes showed significant increases (3.7 to 5.4-fold) in DBA/2FG-pcy mice compared to controls.
- Conversely, epidermal growth factor (EGF) mRNA levels decreased with age in DBA/2FG-pcy mice.
Conclusions:
- The observed downregulation of EGF and upregulation of PCNA, TGF-beta, PDGF, IGF-I, and bFGF mRNA likely contribute to the development and progression of kidney cysts in DBA/2FG-pcy mice.
- These findings offer insights into the molecular mechanisms underlying polycystic kidney disease.
- The study highlights potential therapeutic targets for managing kidney disease progression.