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1.25(OH)2D3 decreases PCNA and mTOR expression and alleviates renal injury in Thy-1 nephritis rat model
Jian-Feng Li1, Lei Jin2, Huan Ma3
1Department of Nephrology, The First People's Hospital of Nanyang City, Nanyang, Henan Province, China.
Objective:
This study investigated the role and mechanisms of 1.25(OH)2D3 in proliferative glomerulonephritis and its effect on the regulation of mesangial cells.
Methods:
Sixty male SD rats were randomly divided into four groups: control (CG), nephritis (NG), nephritis + 1.25(OH)2D3(NVG), and nephritis + 1.25(OH)2D3+ rapamycin (NVRG) (n = 15 per group). Three rats from each group were sacrificed on days 1, 3, 7, 14, and 21 after intervention. Urine samples were collected over 24 hours on day 0 to measure urinary protein excretion. Renal tissue samples were stained with HE and PAS to evaluate the extent of renal injury, while immunohistochemistry was employed to quantify PCNA and mTOR expression in the renal tissues.
Results:
Compared to the NG, mesangial cell proliferation in the renal tissues was significantly reduced in the NVG and NVRG at all time points (all p<0.05). PCNA expressionwas significantly higher in the NG compared to the CG (p < 0.05) and significantly lower in the NVG and NVRG (p < 0.05). mTOR expression was also significantly increased in the NG compared to the CG, with a significant reduction observed in the NVG and NVRG compared to the NG.
Conclusion:
Our findings demonstrate that 1.25(OH)2D3significantly inhibits the proliferation of glomerular mesangial cells in rats. Additionally, mTOR protein is involved in the regulation of glomerular mesangial cells by 1.25(OH)2D3. These results further elucidate the molecular mechanism by which 1.25(OH)2D3alleviates renal injury in glomerulonephritis.
Insights
This study shows that 1.25(OH)2D3 significantly reduces mesangial cell proliferation in proliferative glomerulonephritis. It also reveals the involvement of mTOR protein in this process, clarifying how 1.25(OH)2D3 alleviates renal injury.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Proliferative glomerulonephritis is characterized by mesangial cell proliferation.
- 1.25(OH)2D3 is a vitamin D metabolite with potential therapeutic roles.
Purpose of the Study:
- To investigate the role and mechanisms of 1.25(OH)2D3 in proliferative glomerulonephritis.
- To determine its effect on mesangial cell regulation.
Main Methods:
- A rat model of proliferative glomerulonephritis was established.
- Rats were treated with 1.25(OH)2D3 and/or rapamycin.
- Renal injury, mesangial cell proliferation (PCNA), and mTOR expression were assessed.
Main Results:
- 1.25(OH)2D3 significantly reduced mesangial cell proliferation and PCNA expression.
- mTOR expression was increased in nephritis and reduced by 1.25(OH)2D3 treatment.
- These effects were observed across multiple time points post-intervention.
Conclusions:
- 1.25(OH)2D3 effectively inhibits glomerular mesangial cell proliferation in glomerulonephritis.
- The mammalian target of rapamycin (mTOR) pathway is implicated in the mechanism of action of 1.25(OH)2D3.
- These findings highlight 1.25(OH)2D3 as a potential therapeutic agent for glomerulonephritis.
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