Vitamin D- VDR (vitamin D receptor) alleviates glucose metabolism reprogramming in lipopolysaccharide-induced acute kidney injury.
Frontiers in physiology(2023)
摘要
Our previous study showed that vitamin D (VD)-vitamin D receptor () plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI. To investigate the role of VD- in glucose metabolism reprogramming in LPS-induced AKI. We established a model of LPS-induced AKI in knockout (-KO) mice, renal proximal tubular-specific -overexpressing (-OE) mice and wild-type C57BL/6 mice. , human proximal tubular epithelial cells (HK-2 cells), knockout and overexpression HK-2 cell lines were used. Paricalcitol (an active vitamin D analog) or -OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in -KO mice. In experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-). Moreover, paricalcitol activated the phosphorylation of -activated protein kinase (), and an inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells. VD- alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of phosphorylation the pathway.
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关键词
AMPK pathway,PDHA1 phosphorylation,acute kidney injury,glucose metabolism reprogramming,vitamin D,vitamin D receptor
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