Metabolism: clinical and experimental · 2025
Syndecan-1 regulates lipid metabolism and mitigates fibrosis during the transition from acute kidney injury to chronic kidney disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shen Daoqi, Lin Liyu, Su Yiqi, Huang Ying, Wang Yaqiong, Xu Jiarui, Jiang Wuhua, Zhang Zhen, Ding Xiaoqiang, Xu Xialian
Аннотация
BACKGROUND: The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is characterized by persistent renal fibrosis, in which abnormal lipid metabolism plays a crucial role. Syndecan-1 (SDC-1) has been implicated in various tissue remodeling processes; however, its role in lipid metabolism and fibrosis during the progression from AKI to CKD is not well understood.
METHODS: This study used a murine model of unilateral ischemia-reperfusion-induced AKI-to-CKD progression for in vivo analysis and employed transforming growth factor-beta (TGF-β)-induced fibrosis in Human Kidney-2 cells and primary mouse tubular epithelial cells for in vitro studies. The tubule-specific knockout and overexpression of SDC-1 mice were utilized to investigate kidney fibrosis and lipid metabolism.
RESULTS: Following unilateral ischemia-reperfusion and TGF-β stimulation, SDC-1 expression was significantly reduced, exacerbating renal fibrosis. Notably, SDC-1 deficiency led to lipid accumulation in the kidneys, while its overexpression alleviated lipid overload and improved metabolic parameters. Furthermore, SDC-1 played a crucial role in regulating fatty acid-binding protein 7 (FABP7), and its absence resulted in increased FABP7 levels. Inhibition of FABP7 not only reduced fibrosis but also restored carnitine palmitoyltransferase 1α expression, which suggests that the SDC-1/FABP7 axis is critical for maintaining lipid homeostasis and mitigating fibrosis in the kidney.
CONCLUSION: These findings underscore the importance of SDC-1 in lipid metabolism and suggest that targeting lipid metabolic pathways may represent therapeutic strategies that can slow the progression of AKI to CKD.
METHODS: This study used a murine model of unilateral ischemia-reperfusion-induced AKI-to-CKD progression for in vivo analysis and employed transforming growth factor-beta (TGF-β)-induced fibrosis in Human Kidney-2 cells and primary mouse tubular epithelial cells for in vitro studies. The tubule-specific knockout and overexpression of SDC-1 mice were utilized to investigate kidney fibrosis and lipid metabolism.
RESULTS: Following unilateral ischemia-reperfusion and TGF-β stimulation, SDC-1 expression was significantly reduced, exacerbating renal fibrosis. Notably, SDC-1 deficiency led to lipid accumulation in the kidneys, while its overexpression alleviated lipid overload and improved metabolic parameters. Furthermore, SDC-1 played a crucial role in regulating fatty acid-binding protein 7 (FABP7), and its absence resulted in increased FABP7 levels. Inhibition of FABP7 not only reduced fibrosis but also restored carnitine palmitoyltransferase 1α expression, which suggests that the SDC-1/FABP7 axis is critical for maintaining lipid homeostasis and mitigating fibrosis in the kidney.
CONCLUSION: These findings underscore the importance of SDC-1 in lipid metabolism and suggest that targeting lipid metabolic pathways may represent therapeutic strategies that can slow the progression of AKI to CKD.