PDF(Pubmed)
Abstract：
UNASSIGNED: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis.
UNASSIGNED: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.
UNASSIGNED: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.
UNASSIGNED: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
UNASSIGNED: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.
UNASSIGNED: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.
UNASSIGNED: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
摘要：
■肾脂代谢异常导致肾脂沉积，导致糖尿病肾病（DKD）中肾脏纤维化的发展。本研究旨在探讨绿原酸(CA)降低肾脏脂质蓄积、改善DKD肾纤维化的作用及机制。
■这项研究评估了CA对肾脏纤维化的影响，通过构建DKD的体内外模型，脂质沉积和脂质代谢，并检测Notch1和Stat3信号通路的改善。分子对接用于预测CA与Notch1蛋白胞外结构域NRR1之间的结合。
■体外研究表明，CA降低了纤连蛋白的表达，α-平滑肌肌动蛋白（α-SMA），p-smad3/smad3，减轻脂质沉积，促进肉碱棕榈酰转移酶1A（CPT1A）的表达，抑制胆固醇调节元件结合蛋白1c(SREBP1c)的表达。Notch1、CleavedNotch1、Hes1和p-stat3/stat3的表达受到抑制。这些结果表明，CA可能通过抑制Notch1和stat3信号通路减少人肾细胞（HK2）的细胞间脂质沉积，从而改善纤维化。Further,体内研究表明，CA通过抑制Notch1和stat3信号通路改善DKD小鼠的肾纤维化和肾脏脂质沉积。最后,分子对接实验表明,CA与NRR1的结合能为-6.6kcal/mol,初步预测了CA对Notch1胞外结构域NRR1的可能作用。
■CA通过抑制Notch1和stat3信号通路减少肾脏脂质积累并改善DKD肾脏纤维化。
■这项研究评估了CA对肾脏纤维化的影响，通过构建DKD的体内外模型，脂质沉积和脂质代谢，并检测Notch1和Stat3信号通路的改善。分子对接用于预测CA与Notch1蛋白胞外结构域NRR1之间的结合。
■体外研究表明，CA降低了纤连蛋白的表达，α-平滑肌肌动蛋白（α-SMA），p-smad3/smad3，减轻脂质沉积，促进肉碱棕榈酰转移酶1A（CPT1A）的表达，抑制胆固醇调节元件结合蛋白1c(SREBP1c)的表达。Notch1、CleavedNotch1、Hes1和p-stat3/stat3的表达受到抑制。这些结果表明，CA可能通过抑制Notch1和stat3信号通路减少人肾细胞（HK2）的细胞间脂质沉积，从而改善纤维化。Further,体内研究表明，CA通过抑制Notch1和stat3信号通路改善DKD小鼠的肾纤维化和肾脏脂质沉积。最后,分子对接实验表明,CA与NRR1的结合能为-6.6kcal/mol,初步预测了CA对Notch1胞外结构域NRR1的可能作用。
■CA通过抑制Notch1和stat3信号通路减少肾脏脂质积累并改善DKD肾脏纤维化。
