Li Jian-Feng, Jin Lei, Ma Huan, Suo Jie, Yang Rui, Yang Xiao-Ping
Department of Nephrology, The First People's Hospital of Nanyang City, Nanyang, Henan Province, China.
Department of Rheumatology, Immunology & Allergy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2024 Dec 5;19(12):e0311000. doi: 10.1371/journal.pone.0311000. eCollection 2024.
This study investigated the role and mechanisms of 1.25(OH)2D3 in proliferative glomerulonephritis and its effect on the regulation of mesangial cells.
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.
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.
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.
本研究探讨1,25(OH)₂D₃在增殖性肾小球肾炎中的作用及机制，以及其对系膜细胞调节的影响。
将60只雄性SD大鼠随机分为四组：对照组（CG）、肾炎组（NG）、肾炎 + 1,25(OH)₂D₃组（NVG）和肾炎 + 1,25(OH)₂D₃ + 雷帕霉素组（NVRG）（每组n = 15）。干预后第1、3、7、14和21天，每组处死3只大鼠。在第0天收集24小时尿液样本以测量尿蛋白排泄量。肾组织样本用HE和PAS染色以评估肾损伤程度，同时采用免疫组织化学法对肾组织中PCNA和mTOR表达进行定量分析。
与NG组相比，NVG组和NVRG组在所有时间点肾组织中的系膜细胞增殖均显著降低（均p<0.05）。与CG组相比，NG组中PCNA表达显著更高（p < 0.05），而在NVG组和NVRG组中显著更低（p < 0.05）。与CG组相比，NG组中mTOR表达也显著增加，与NG组相比，NVG组和NVRG组中mTOR表达显著降低。
我们的研究结果表明，1,25(OH)₂D₃显著抑制大鼠肾小球系膜细胞的增殖。此外，mTOR蛋白参与1,25(OH)₂D₃对肾小球系膜细胞的调节。这些结果进一步阐明了1,25(OH)₂D₃减轻肾小球肾炎肾损伤的分子机制。
