Treffer: Axl‐inhibitor bemcentinib alleviates mitochondrial dysfunction in the unilateral ureter obstruction murine model.

Renal fibrosis is a progressive histological manifestation leading to chronic kidney disease (CKD) and associated with mitochondrial dysfunction. In previous work, we showed that Bemcentinib, an Axl receptor tyrosine kinase inhibitor, reduced fibrosis development. In this study, to investigate its effects on mitochondrial dysfunction in renal fibrosis, we analysed genome‐wide transcriptomics data from a unilateral ureter obstruction (UUO) murine model in the presence or absence of bemcentinib (n = 6 per group) and SHAM‐operated (n = 4) mice. Kidney ligation resulted in dysregulation of mitochondria‐related pathways, with a significant reduction in the expression of oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), citric acid cycle (TCA), response to reactive oxygen species and amino acid metabolism‐related genes. Bemcentinib treatment increased the expression of these genes. In contrast, AKT/PI3K signalling pathway genes were up‐regulated upon UUO, but bemcentinib largely inhibited their expression. At the functional level, ligation reduced mitochondrial biomass, which was increased upon bemcentinib treatment. Serum metabolomics analysis also showed a normalizing amino acid profile in UUO, compared with SHAM‐operated mice following bemcentinib treatment. Our data suggest that mitochondria and mitochondria‐related pathways are dramatically affected by UUO surgery and treatment with Axl‐inhibitor bemcentinib partially reverses these effects. [ABSTRACT FROM AUTHOR]

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