Ghrelin Protects against Renal Damages Induced by Angiotensin-II via an Antioxidative Stress Mechanism in MiceReportar como inadecuado




Ghrelin Protects against Renal Damages Induced by Angiotensin-II via an Antioxidative Stress Mechanism in Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

We explored the renal protective effects by a gut peptide, Ghrelin. Daily peritoneal injection with Ghrelin ameliorated renal damages in continuously angiotensin II AngII-infused C57BL-6 mice as assessed by urinary excretion of protein and renal tubular markers. AngII-induced increase in reactive oxygen species ROS levels and senescent changes were attenuated by Ghrelin. Ghrelin also inhibited AngII-induced upregulations of transforming growth factor-β TGF-β and plasminogen activator inhibitor-1 PAI-1, ameliorating renal fibrotic changes. These effects were accompanied by concomitant increase in mitochondria uncoupling protein, UCP2 as well as in a key regulator of mitochondria biosynthesis, PGC1α. In renal proximal cell line, HK-2 cells, Ghrelin reduced mitochondria membrane potential and mitochondria-derived ROS. The transfection of UCP2 siRNA abolished the decrease in mitochondria-derived ROS by Ghrelin. Ghrelin ameliorated AngII-induced renal tubular cell senescent changes and AngII-induced TGF-β and PAI-1 expressions. Finally, Ghrelin receptor, growth hormone secretagogue receptor GHSR-null mice exhibited an increase in tubular damages, renal ROS levels, renal senescent changes and fibrosis complicated with renal dysfunction. GHSR-null mice harbored elongated mitochondria in the proximal tubules. In conclusion, Ghrelin suppressed AngII-induced renal damages through its UCP2 dependent anti-oxidative stress effect and mitochondria maintenance. Ghrelin-GHSR pathway played an important role in the maintenance of ROS levels in the kidney.



Autor: Keiko Fujimura, Shu Wakino , Hitoshi Minakuchi, Kazuhiro Hasegawa, Koji Hosoya, Motoaki Komatsu, Yuka Kaneko, Keisuke Shinozuka,

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados