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. 2021 Feb;236(2):931-945.
doi: 10.1002/jcp.29903. Epub 2020 Jun 24.

Involvement of GPX4 in irisin's protection against ischemia reperfusion-induced acute kidney injury

Jia Zhang  1   2 , Jianbin Bi  1   2 , Yifan Ren  1   2 , Zhaoqing Du  1   2 , Teng Li  1   2 , Tao Wang  1   2 , Lin Zhang  1   2 , Mengzhou Wang  1   2 , Shasha Wei  1   2 , Yi Lv  1   2 , Rongqian Wu  1
Affiliations

Involvement of GPX4 in irisin's protection against ischemia reperfusion-induced acute kidney injury

Jia Zhang et al. J Cell Physiol. 2021 Feb.

Abstract

Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/R-induced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 μg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.

Keywords: AKI; GPX4; ROS; irisin; renal I/R.

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