DDRGK1-mediated ER-phagy attenuates acute kidney injury through ER-stress and apoptosis.
Haijiao JinYuanting YangXuying ZhuYin ZhouYao XuJialin LiChaojun QiXinghua ShaoJingkui WuShan WuHong CaiLeyi GuShan MouZhaohui NiShu LiQisheng LinPublished in: Cell death & disease (2024)
Acute kidney injury (AKI) constitutes a prevalent clinical syndrome characterized by elevated morbidity and mortality rates, emerging as a significant public health issue. This study investigates the interplay between endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and ER-associated degradation (ER-phagy) in the pathogenesis of AKI. We employed four distinct murine models of AKI-induced by contrast media, ischemia-reperfusion injury, cisplatin, and folic acid-to elucidate the relationship between ER-phagy, ER stress, and apoptosis. Our findings reveal a marked decrease in ER-phagy coinciding with an accumulation of damaged ER, elevated ER stress, and increased apoptosis across all AKI models. Importantly, overexpression of DDRGK1 in HK-2 cells enhanced ER-phagy levels, ameliorating contrast-induced ER stress and apoptosis. These findings unveil a novel protective mechanism in AKI, wherein DDRGK1-UFL1-mediated ER-phagy mitigates ER stress and apoptosis in renal tubular epithelial cells. Our results thereby contribute to understanding the molecular underpinnings of AKI and offer potential therapeutic targets for its treatment.
Keyphrases
- endoplasmic reticulum
- acute kidney injury
- cell cycle arrest
- cardiac surgery
- oxidative stress
- endoplasmic reticulum stress
- estrogen receptor
- cell death
- public health
- induced apoptosis
- breast cancer cells
- ischemia reperfusion injury
- pi k akt
- diabetic rats
- radiation therapy
- dna methylation
- risk assessment
- single cell
- radiation induced
- replacement therapy