Targeting Endoplasmic Reticulum for Novel Therapeutics and Monitoring in Acute Kidney Injury

Background: Endoplasmic reticulum (ER) stress response is a conservative mechanism involving a complex network of different molecular branches to determine cell fate through specific transcription factors and downstream executors. Emerging evidence shows that ER stress is implicated in the occurrence and progression of acute kidney injury (AKI) in different animal models and human patients. However, there is still a lack of therapeutics targeting the ER in AKI. Summary: Several therapeutic chemicals, including a compound that induces activating transcription factor 6 (ATF6) and chemical chaperones, have been developed to target the ER in the treatment of AKI. Meanwhile, ER stress-inducible secreted proteins, mesencephalic astrocyte-derived neurotrophic factor (MANF), and cysteine-rich with EGF-like domains 2 (CRELD2) could serve as potential ER stress biomarkers in the early diagnosis and treatment response monitoring of human patients with AKI. Key Messages: Experimental and clinical evidence suggests the critical role of ER in the pathogenesis and progression of AKI, and ER is a novel target in AKI therapy.