Open AccessAugmenter of liver regeneration protects the kidney from ischaemia‐reperfusion injury in ferroptosis
Author(s) -
Huang Lili,
Liao Xiaohui,
Sun Hang,
Jiang Xiao,
Liu Qi,
Zhang Ling
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14302
Subject(s) - reactive oxygen species , gene silencing , programmed cell death , glutathione , kidney , small hairpin rna , oxidative stress , gpx4 , microbiology and biotechnology , biology , reperfusion injury , cancer research , small interfering rna , chemistry , ischemia , rna , medicine , apoptosis , glutathione peroxidase , biochemistry , enzyme , endocrinology , gene
Acute kidney injury ( AKI ) is a common and severe clinical condition with high morbidity and mortality. Ischaemia‐reperfusion (I/R) injury remains the major cause of AKI in the clinic. Ferroptosis is a recently discovered form of programmed cell death ( PCD ) that is characterized by iron‐dependent accumulation of reactive oxygen species ( ROS ). Compelling evidence has shown that renal tubular cell death involves ferroptosis, although the underlying mechanisms remain unclear. Augmenter of liver regeneration ( ALR ) is a widely distributed multifunctional protein that is expressed in many tissues. Our previous study demonstrated that ALR possesses an anti‐oxidant function. However, the modulatory mechanism of ALR remains unclear and warrants further investigation. Here, to elucidate the role of ALR in ferroptosis, ALR expression was inhibited using short hairpin RNA lentivirals (sh RNA ) in vitro model of I/R‐induced AKI . The results suggest that the level of ferroptosis is increased, particularly in the sh RNA / ALR group, accompanied by increased ROS and mitochondrial damage. Furthermore, inhibition of system xc‐ with erastin aggravates ferroptosis, particularly silencing of the expression of ALR . Unexpectedly, we demonstrate a novel signalling pathway of ferroptosis. In summary, we show for the first time that silencing ALR aggravates ferroptosis in an in vitro model of I/R. Notably, we show that I/R induced kidney ferroptosis is mediated by ALR , which is linked to the glutathione‐glutathione peroxidase ( GSH ‐ GP x) system.