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

被引：40

作者：

Fujimura, Keiko ^{[1
]}

Wakino, Shu ^{[1
]}

Minakuchi, Hitoshi ^{[1
]}

Hasegawa, Kazuhiro ^{[1
]}

Hosoya, Koji ^{[1
]}

Komatsu, Motoaki ^{[1
]}

Kaneko, Yuka ^{[1
]}

Shinozuka, Keisuke ^{[1
]}

Washida, Naoki ^{[1
]}

Kanda, Takeshi ^{[1
]}

Tokuyama, Hirobumi ^{[1
]}

Hayashi, Koichi ^{[1
]}

Itoh, Hiroshi ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan

来源：

PLOS ONE | 2014年 / 9卷 / 04期

关键词：

ACUTE KIDNEY INJURY; MITOCHONDRIAL BIOGENESIS; UNCOUPLING PROTEIN-2; ACYLATED PEPTIDE; SKELETAL-MUSCLE; BLOOD-VESSELS; GROWTH; SENESCENCE; EXPRESSION; OVEREXPRESSION;

D O I：

10.1371/journal.pone.0094373

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-beta (TGF-beta) 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, PGC1 alpha. 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-beta 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.

引用

页数：15

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