Nitta K, Uchida K, Kimata N, Kawashima A, Yumura W, Nihei H
Department of Medicine, Tokyo Women's Medical College, Japan.
Eur J Pharmacol. 1995 Dec 7;293(4):491-4. doi: 10.1016/s0014-2999(95)80109-x.
These experiments were performed in an attempt to determine whether chronic stimulation of glomerular endothelial cells with recombinant human erythropoietin would alter mesangial cell proliferation. Glomerular endothelial cells in culture incubated with various concentrations of erythropoietin for up to 4 days exhibited dose-dependent endothelin-1 production. Moreover, the conditioned medium from erythropoietin-stimulated glomerular endothelial cells enhanced [3H]thymidine incorporation into mesangial cells. This enhancement was significantly attenuated in the presence of a endothelin A receptor antagonist, BQ-123. These results suggest that endothelin-1 mediates erythropoietin-stimulated glomerular endothelial cell-dependent mesangial cell proliferation, resulting in the progression of glomerulonephritis.
进行这些实验是为了确定用重组人促红细胞生成素长期刺激肾小球内皮细胞是否会改变系膜细胞增殖。培养的肾小球内皮细胞与不同浓度的促红细胞生成素孵育长达4天,呈现出剂量依赖性的内皮素-1产生。此外,促红细胞生成素刺激的肾小球内皮细胞的条件培养基增强了[3H]胸苷掺入系膜细胞。在存在内皮素A受体拮抗剂BQ-123的情况下,这种增强作用显著减弱。这些结果表明,内皮素-1介导促红细胞生成素刺激的肾小球内皮细胞依赖性系膜细胞增殖,从而导致肾小球肾炎的进展。