02.10.2024 Glucocorticoid receptor activation aggravates renal injury

Acute kidney injury (AKI) is a frequent and challenging clinical problem associated with high morbidity and mortality. In the acutely injured kidney, repair mechanisms are activated to restore tissue homeostasis, and AKI can therefore be reversible. However, if the renal stress response is maladaptive, then AKI can exacerbate and progress to chronic kidney disease. In AKI, renal tubular epithelial cells (TECs) are the major site of injury and exhibit pronounced plasticity to adapt to stress conditions, to adopt a proliferative state, and to repair damaged tubules. Consistent with their importance in AKI, TECs also play decisive roles in maladaptive processes. Here, we show that injury of renal TECs induces activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravates, rather than alleviates, TEC injury. This adverse effect is exacerbated by exogenously administered glucocorticoids. Mechanistically, our results show that GR signaling in injured TECs controls a maladaptive transcriptional program to impede DNA repair and hamper mitochondrial bioenergetics. These findings may have important translational implications for the use of glucocorticoids in patients with AKI. 

Link to publication: Luping Zhou, Marc Torres Pereiro, Thomas Worzfeld et al. Glucocorticoids induce a maladaptive epithelial stress response to aggravate acute kidney injury.Sci. Transl. Med.16,eadk5005(2024).