When two signals cross paths: cGAS-STING and ER stress in kidney disease progression

Abstract

Previous reports have suggested that both the endoplasmic reticulum (ER) stress and cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes pathways contribute to the progression of chronic kidney disease; however, the relationship between these 2 pathways in kidney injury has not been fully elucidated. Andrade-Silva et al. revealed that the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes pathway can enhance ER stress through the protein kinase R-like ER kinase (PERK)–mediated signaling cascade in kidney tubular epithelial cells and sequentially augment fibrosis during kidney injury. Further studies are needed to elucidate the precise mechanisms by which the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes pathway activates PERK-dependent ER stress in kidney tubular epithelial cells post injury.