Research Paper Volume 11, Issue 6 pp 1804—1820

Endothelial cells secreted endothelin-1 augments diabetic nephropathy via inducing extracellular matrix accumulation of mesangial cells in ETBR-/- mice

Figure 8. Inhibition of NF-kappaB pathway ameliorated DN in ETBR-/- mice in vivo. (A-C) C57BL/6 mice, ETBR-/- mice were intraperitoneally injected with 50 mg/kg STZ every day for five days to establish STZ-diabetic mice model. Bay (1 mg/kg, Bay 11-7082) was dissolved in normal saline, and injected intraperitoneally twice a week between seventh and tenth weeks after STZ treatment. Y27632 (5 mg/kg, Rhoa/Rock inhibitor) was injected intraperitoneally twice a week between seventh and tenth weeks after STZ treatment. Serum creatinine, urinary albumin, serum ET-1 and kidney ET-1 were detected in WT, WT+Bay, WT+Y27632, ETBR-/-, ETBR-/-+Bay and ETBR-/-+Y27632 mice groups. **p<0.01 compared with WT or ETBR-/-. Bars depict the mean ± SD. N=6. (D) PAS staining showed that enlargement of glomeruli was observed in STZ-diabetic mice, and glomerulosclerosis was relieved in Bay and Y27632 treated WT or ETBR-/- mice. **p<0.01 compared with STZ WT or STZ ETBR-/-. 1000×magnification. (E) MASSON staining showed that collagen was produced in glomeruli in STZ-diabetic mice, and the formation of collagen was relieved in Bay and Y27632 treated WT or ETBR-/- mice. 1000×magnification. (F) Cascade diagram of signaling pathways.