Role of peroxisomes in the pathogenesis and therapy of renal fibrosis

Abstract

Renal fibrosis is a pathological consequence of end-stage chronic kidney disease, driven by factors such as oxidative stress, dysregulated fatty acid metabolism, extracellular matrix (ECM) imbalance, and epithelial-to-mesenchymal transition. Peroxisomes play a critical role in fatty acid β-oxidation and the scavenging of reactive oxygen species, interacting closely with mitochondrial functions. Nonetheless, current research often prioritizes the mitochondrial influence on renal fibrosis, often overlooking the contribution of peroxisomes. This comprehensive review systematically elucidates the fundamental biological functions of peroxisomes and delineates the molecular mechanisms underlying peroxisomal dysfunction in renal fibrosis pathogenesis. Here, we discuss the impact of peroxisome dysfunction and pexophagy on oxidative stress, ECM deposition, and renal fibrosis in various cell types including mesangial cells, endothelial cells, podocytes, epithelial cells, and macrophages. Furthermore, this review highlights the recent advancements in peroxisome-targeted therapeutic strategies to alleviate renal fibrosis.