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The protective role of intermedin in promoting angiogenesis during renal fibrosis

Dong, Honglin, Zhou, Yun, Wang, Yanhon, Zhou, Qin, Zhang, Yan, Gan, Xiaofang, Luo, Yankong, Li, Rongshan
Gene 2019 v.688 pp. 34-43
angiogenesis, animal models, blood, blood flow, fibrosis, heart, kidney diseases, protective effect, rats, renal tubules, surgery, vascular endothelial growth factor receptors
Renal fibrosis promotes the progression of chronic renal disease to end-stage renal disease. Microvascular damage and loss play an important role in renal fibrosis. Intermedin (IMD) is expressed mainly in the heart and kidney. IMD has been shown to increase renal blood flow and reduce the loss of glomerular and surrounding renal tubules, but its role in mediating microvascular damage in renal fibrosis remains to be elucidated. Here, we investigated the effects of IMD on microvascular damage in a renal fibrosis model.We created a rat model of unilateral ureteral obstruction (UUO) to clarify the effect of microvascular damage on renal fibrosis and the effect of intermedin on reversing renal vascular injury and promoting angiogenesis. Rats were divided randomly into three groups: sham, UUO, and UUO + IMD. The sham group underwent free ureteral ligation but not occlusion. Rats in the latter two groups underwent UUO, and rats in the IMD group were additionally administered intermedin (100 ng/kg/h) daily. On the 7th, 14th, 21st, and 28th days after surgery, abdominal aortic blood and the obstructed kidneys were harvested from the rats (n = 6) for analysis.IMD was found to protect against renal vascular injury and to increase microvessel density. Molecularly, IMD upregulated vascular endothelial growth factor–vascular endothelial growth factor receptor (VEGF–VEGFR2) pathway activity. The VEGF–VEGFR2 pathway might be the underlying mechanism mediating the protective activities of IMD in promoting angiogenesis, delaying renal fibrosis, and improving renal function.IMD could be a potential candidate treatment for renal fibrosis.