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Kidney Week

Abstract: PO1707

VEGFA-Angpt-Tie2 Participates in the Interaction Between Mesangial Cells and Glomerular Endothelial Cells in Rat Anti-Thy-1 Nephritis

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Wu, Lingling, Chinese PLA General Hospital and Military Medical Postgraduate College, Beijing, China
  • Zhao, Yinghua, Chinese PLA General Hospital and Military Medical Postgraduate College, Beijing, China
  • Wu, Jie, Chinese PLA General Hospital and Military Medical Postgraduate College, Beijing, China
  • Chen, Xiangmei, Chinese PLA General Hospital and Military Medical Postgraduate College, Beijing, China
Background

Mesangial cells and glomerular endothelial cells, as the renal intrinsic cells,are involved in the occurrence and development of various kidney diseases. In mesangial proliferative glomerulonephritis, the endothelial cells are affected by the signals from mesangial cells and show pathological changes such as diffuse capillary proliferation. But the specific signaling pathway mechanism is still unclear.

Methods

By establishing the rat model of anti-Thy-1 nephritis,and co-culturing mesangial cells and endothelial cells in the transwell system.

Results

By establishing the rat model of anti-Thy-1 nephritis, we found that the damage of mesangial cells in the glomeruli was accompanied by the proliferation of diffuse endothelial cells on the 7th day. Furthermore, we found that activated mesangial cells can promote endothelial cell proliferation and migration through co-culturing mesangial cells and endothelial cells in the transwell system, and vice versa. VEGFA expression was increased in activated mesangial cells, which promoted the expression of Angpt2 in endothelial cells. Angpt2 binds to Tie2, the endothelial cell surface receptor, and inhibits the phosphorylation of Tie2, thereby causing endothelial cell proliferation. When VEGFA neutralizing antibody was added into the co-culture system, the expression level of Angpt2 in endothelial cells decreased, the phosphorylation level of Tie2 increased, and cell proliferation was inhibited. If Angpt1 was added into the co-culture system and combined with Tie2, the effect of Angpt2 could be competitively inhibited, and the endothelial cell proliferation could be alleviated. In addition, after we injected Angpt1 into rats of anti-Thy-1 nephritis, the expression of Angpt2 in glomeruli decreased, the phosphorylation level of Tie2 increased, and the proliferation of endothelial cells decreased significantly.

Conclusion

The above results suggest that VEGFA-Angpt-Tie2 signaling pathway is involved in the interaction between mesangial cells and endothelial cells in mesangial proliferative glomerulonephritis. Angpt1 can be used as a new method to treat mesangial proliferative glomerulonephritis.