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Immunometabolic rewiring of tubular epithelial cells in kidney disease
Nature Reviews Nephrology ( IF 28.6 ) Pub Date : 2022-07-07 , DOI: 10.1038/s41581-022-00592-x
Sanne van der Rijt 1, 2, 3 , Jaklien C Leemans 1 , Sandrine Florquin 1, 4 , Riekelt H Houtkooper 2, 3, 5 , Alessandra Tammaro 1, 4
Affiliation  

Kidney tubular epithelial cells (TECs) have a crucial role in the damage and repair response to acute and chronic injury. To adequately respond to constant changes in the environment, TECs have considerable bioenergetic needs, which are supported by metabolic pathways. Although little is known about TEC metabolism, a number of ground-breaking studies have shown that defective glucose metabolism or fatty acid oxidation in the kidney has a key role in the response to kidney injury. Imbalanced use of these metabolic pathways can predispose TECs to apoptosis and dedifferentiation, and contribute to lipotoxicity and kidney injury. The accumulation of lipids and aberrant metabolic adaptations of TECs during kidney disease can also be driven by receptors of the innate immune system. Similar to their actions in innate immune cells, pattern recognition receptors regulate the metabolic rewiring of TECs, causing cellular dysfunction and lipid accumulation. TECs should therefore be considered a specialized cell type — like cells of the innate immune system — that is subject to regulation by immunometabolism. Targeting energy metabolism in TECs could represent a strategy for metabolically reprogramming the kidney and promoting kidney repair.



中文翻译:

肾病肾小管上皮细胞的免疫代谢重新布线

肾小管上皮细胞 (TEC) 在急性和慢性损伤的损伤和修复反应中起着至关重要的作用。为了充分应对环境的不断变化,TEC 具有相当大的生物能量需求,这些需求得到代谢途径的支持。尽管对 TEC 代谢知之甚少,但许多开创性研究表明,肾脏中的葡萄糖代谢缺陷或脂肪酸氧化在对肾损伤的反应中起着关键作用。这些代谢途径的不平衡使用会使 TEC 易于凋亡和去分化,并导致脂肪毒性和肾损伤。肾脏疾病期间 TEC 的脂质积累和异常代谢适应也可以由先天免疫系统的受体驱动。类似于它们在先天免疫细胞中的作用,模式识别受体调节 TEC 的代谢重新布线,导致细胞功能障碍和脂质积累。因此,TECs 应该被认为是一种特殊的细胞类型——就像先天免疫系统的细胞一样——受免疫代谢的调节。靶向 TEC 中的能量代谢可能代表一种对肾脏进行代谢重编程和促进肾脏修复的策略。

更新日期:2022-07-07
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