IL-22-mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury

Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end-stage renal disease (ESTD). Interleukin-22 (IL-22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here, we first provide evidence that IL-22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL-22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL-22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL-22 are certificated in cisplatin-induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL-22 on kidneys and highlight the therapeutic opportunities of IL-22 and the involved metabolic regulators in various kidney diseases.

Automated summary

The study shows that interleukin-22 (IL-22) can attenuate kidney injury by reprogramming the metabolism of renal tubular epithelial cells (TECs) and alleviating mitochondrial reactive oxygen species (ROS) accumulation. IL-22 improves kidney function in cisplatin-induced kidney damage and diabetic nephropathy (DN) animal models by inducing AMPK/AKT signaling and PFBFK3 activities.