Endothelial CPT2 loss impairs fatty acid oxidation and promotes renal fibrosis

Figures

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  Figure 1. Endothelial FAO regulates acetyl-CoA, EndoMT, and renal injury. (a) Schematic diagram illustrating how FAO generates acetyl-CoA via CPT2 and how acetate replenishes acetyl-CoA through ACSS2. ACLY, ATP citrate lyase; TCA cycle, tricarboxylic acid cycle. (b) Gene-targeting strategy for conditional deletion of Cpt2 (exon 4 flanked by loxP sites). Viable VE-cadherin Cre-positive offspring from VE-cadherin Cre; Cpt2flox/+ intercrosses showed expected Mendelian ratios. (c and d) CPT2 expression in primary lung endothelial cells from Cpt2E-WT and Cpt2E-KO mice, analyzed by qPCR (c) and western blot (d). n = 3 independent experiments. (e) Relative ATP levels in Cpt2E-WT and Cpt2E-KO endothelial cells (n = 3). (f) qPCR analysis showing that heterologous Cpt2 expression suppresses EndoMT marker induction in Cpt2E-KO endothelial cells (n = 3). (g) qPCR analysis showing that acetate supplementation inhibits EndoMT marker expression in Cpt2E-KO cells (n = 3). (h–j) Renal injury in Cpt2E-WT and Cpt2E-KO kidneys, assessed by KIM-1 mRNA (h; n = 5 mice per genotype) and protein levels (i and j; n = 6 mice per genotype). (k and l) Representative Masson’s trichrome-stained kidney sections (k) and…