Transient hypoxia-inducible factor activation in rat renal ablation and reduced fibrosis with L-mimosine

摘要: : Aim:  Hypoxia-inducible factor (HIF) activity during the course of chronic kidney disease (CKD) development is poorly defined, and effect HIF activation on CKD still controversial. The purpose present study was to characterize expression development, investigate by using prolyl hydroxylase (PHD) inhibitor L-mimosine. Methods:  Rats with remnant kidneys (RK) were killed at week 1, 2, 4, 6, 8, 12 after subtotal nephrectomy. An additional group RK rats treated L-mimosine HIF-α activation. Results:  Tubulointerstitial hypoxia in began 1 continued, albeit attenuated, until 12, last time point examined. nuclear HIF-1α HIF-2α, as well typical target genes VEGF (vascular endothelial growth factor), HO-1 (heme oxygenase-1), GLUT-1 (glucose transporter-1) EPO (erythropoietin), all upregulated early stage when renal function stable, returned basal level later, accompanied impaired interstitial fibrosis. administered from 5 led accumulation HIF-2α proteins, increased VEGF, GLUT-1, improved function. Furthermore, fibrosis markers α-smooth muscle actin (α-SMA) Collagen III, peritubular capillary rarefaction index, significantly decreased treatment. Conclusion:  There a transient following later stages re-activated reduced tubulointerstitial