1.25(OH)2D3 decreases PCNA and mTOR expression and alleviates renal injury in Thy-1 nephritis rat model

PLoS One. 2024 Dec 5;19(12):e0311000. doi: 10.1371/journal.pone.0311000. eCollection 2024.

Abstract

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.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Mesangial Cells / pathology
  • Nephritis / drug therapy
  • Nephritis / metabolism
  • Nephritis / pathology
  • Proliferating Cell Nuclear Antigen* / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • TOR Serine-Threonine Kinases* / metabolism
  • Thy-1 Antigens / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • Proliferating Cell Nuclear Antigen
  • mTOR protein, rat
  • Thy-1 Antigens

Grants and funding

This work was supported by the National Natural Resources Foundation of China (81160090) and Research Project Supported by Xinjiang Production and Construction Corps of China (2009GG59) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.