Targeting tubular epithelial cell metabolism to halt renal fibrosis: current evidence and future directions

Renal fibrosis is a common pathological endpoint of chronic kidney disease, characterized by excessive deposition of extracellular matrix and loss of functional nephrons. Emerging evidence highlights that profound metabolic reprogramming is a hallmark and a fundamental driver of renal fibrosis. Alterations in the central metabolic pathways, including glycolysis, mitochondrial dysfunction and lipid metabolism in tubular epithelial cells promote tubular epithelial cell dysfunction and sustain a pro-fibrotic inflammatory microenvironment. Besides, the metabolic microenvironment, particularly characterized by hypoxia and oxidative stress, plays a critical role in the pathogenesis and progression of renal fibrosis, and targeting the metabolic microenvironment has also emerged as a promising anti-fibrotic strategy. In this review, we summarized the current knowledge and explored the potential of targeting metabolic enzymes or signaling pathways involved in key metabolic pathways may represent a promising strategy to attenuate renal fibrosis. Furthermore, we discussed the contribution of the metabolic microenvironment, including hypoxia and oxidative stress, to the pathogenesis of renal fibrosis.