title: Alteration of Fatty Acid Oxidation in Tubular Epithelial Cells: From Acute Kidney Injury to Renal Fibrogenesis.
abstract: Renal proximal tubular cells are the most energy-demanding cells in the body. The ATP that they use is mostly produced in their mitochondrial and peroxisomal compartments, by the oxidation of fatty acids. When those cells are placed under a biological stress, such as a transient hypoxia, fatty acid oxidation (FAO) is shut down for a period of time that outlasts injury, and carbohydrate oxidation does not take over. Facing those metabolic constraints, surviving tubular epithelial cells exhibit a phenotypic switch that includes cytoskeletal rearrangement and production of extracellular matrix proteins, most probably contributing to acute kidney injury-induced renal fibrogenesis, thence to the development of chronic kidney disease. Here, we review experimental evidence that dysregulation of FAO profoundly affects the fate of tubular epithelial cells, by promoting epithelial-to-mesenchymal transition, inflammation, and eventually interstitial fibrosis. Restoring physiological production of energy is undoubtedly a possible therapeutic approach to unlock the mesenchymal reprograming of tubular epithelial cells in the kidney. In this respect, the benefit of the use of fibrates is uncertain, but new drugs that could specifically target this metabolic pathway, and, hopefully, attenuate renal fibrosis merit future research.
authors: IMSERM UMR_S1155, Rare and Common Kidney Diseases, Remodeling and Tissue Repair, Hôpital Tenon , Paris , France.
authors: Noémie
authors: N
authors: Simon
authors: IMSERM UMR_S1155, Rare and Common Kidney Diseases, Remodeling and Tissue Repair, Hôpital Tenon , Paris , France ; UMR S 1155, UPMC Sorbonne Université Paris 06 , Paris , France.
authors: Alexandre
authors: A
authors: Hertig
keywords: acute kidney injury; chronic kidney diseases; epithelium; fatty acid oxidation; fibroblasts; fibrosis