Abstract: FR-PO228

Effect of Huaier on the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis

Session Information

Category: Cell Biology

  • 202 Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation

Author

  • Chen, Xiangmei, Chinese PLA General Hospital, Beijing, Beijing, China
Background

Mesangial proliferative glomerulonephritis (MsPGN) is one of the common kidney diseases. In this study, we investigated whether aqueous extract of Trametes robiniophila murr (Huaier) could suppress mesangial cell proliferation in rat cells treated with platelet-derived growth factor (PDGF)-BB and in rat model of anti-Thy-1 mesangial proliferative glomerulonephritis, and further explored the possible mechanisms of its antiproliferation effects.

Methods

In Vivo: Thirty Wistar rats were randomly divided into five groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + low-dose of Huaier (HRL); (4) anti-Thy-1 nephritis model + medium-dose of Huaier (HRM); (5) anti-Thy-1 nephritis model + high-dose of Huaier (HRH). Two weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined. Meanwhile, the expression levels of Mxi-1 and PCNA in isolated glomeruli were also tested. In Vitro: Rat mesangial cell viability was measured by CCK8. DNA synthesis and cell proliferation evaluated by with 5-ethynyl-2'-deoxyuridine(Edu) Assay. The distribution of cell cycle, PI-Annexin-V staining was analyzed by flow cytometry, and western blot were used to test the cell cycle pathways.

Results

Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB–stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB–stimulated cells.

Conclusion

Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB–stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.

Funding

  • Government Support - Non-U.S.