Mesenchymal stem cells alleviate palmitic acid-induced endothelial-to-mesenchymal transition by suppressing endoplasmic reticulum stress

Luo, Ruixi; Li, Linzhao; Liu, Xiaohong; Yuan, Yujia; Zhu, Wuzheng; Li, Lan; Liu, Jingping; Liu, Yanrong; Cheng, Jun; Chen, Younan

doi:10.1152/ajpendo.00155.2020

Cited by 21 publications

(20 citation statements)

References 33 publications

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“…Consistent with these results, PA upregulated the LOX-1 expression in HUVECs in our study. To gain insight into the mechanism underlying this effect, we evaluated the contribution of ER stress based on our previous study [ 3 ]. Interestingly, LOX-1 upregulation was alleviated by the ER stress inhibitor TUDCA, suggesting that suppressing ER stress lowers PA-induced LOX-1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…The tube formation assay was assessed using Matrigel Basement Membrane Matrix (BD Biosciences, USA) [ 3 ]. The average number of tubules and dendritic length was calculated using ImageJ Pro Plus software.…”

Section: Methodsmentioning

confidence: 99%

“…Immunofluorescence staining was conducted as described in a previous study [ 3 ]. HUVECs were incubated using an anti-Bip antibody (Proteintech) and an anti-LOX1 antibody (10585-T26; Sino Biological).…”

Section: Methodsmentioning

confidence: 99%

“…Endothelial cell dysfunction, which is the innermost layer of blood vessels, is considered an early indicator of AS [ 2 ]. In a previous study, we showed that palmitic acid (PA) induces lipotoxicity in endothelial cells [ 3 ], which contributes to the early phase of AS pathogenesis. However, the roles and detailed mechanisms of FFAs in the pathogenesis of AS remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…The endoplasmic reticulum (ER) plays a key role in the cellular stress response and is considered a center for lipid and protein synthesis, folding, and assembly. We previously reported that PA induces lipotoxicity via the ER stress pathway in several types of cells, including pancreatic β cells [ 9 ], hepatocytes [ 10 ], and endothelial cells [ 3 ]. Furthermore, additional evidence has shown that ER stress is an initiating factor of lipotoxicity and atherosclerosis [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs

Luo

Zhao

et al. 2021

BioMed Research International

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Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs

Luo

Zhao

et al. 2021

BioMed Research International

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Penthorum chinense Pursh extract ameliorates hepatic steatosis by suppressing pyroptosis via the NLRP3/Caspase‐1/GSDMD pathway

Luo,

Hu,

Wang

et al. 2024

Food Science & Nutrition

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The primary catalyst for nonalcoholic fatty liver disease (NAFLD) is widely recognized as the induction of lipotoxicity in hepatocytes by an excess of fatty acids. In China, Penthorum chinense Pursh (PcP) is commonly employed as a functional food due to its known hepatoprotective properties. The present study aimed to investigate the influence of PcP extract on in vivo and in vitro models of NAFLD. We found that PcP extract can attenuate palmitic acid (PA)‐induced lipotoxicity in HepG2 cells. PA was observed to trigger pyroptosis, as indicated by the increased expression of NLRP3 and GSDMD/N, activation of Caspase‐1, and subsequent release of IL‐1β and IL‐18. However, these changes were reversed after PcP was administered. Furthermore, the application of an NLRP3 agonist inhibited the protective effects of PcP on lipotoxicity, indicating that PcP decreased lipotoxicity by inhibiting the NLRP3/Caspase‐1/GSDMD pathway. Ultimately, we established a rat model of NAFLD through the administration of a high‐fat diet (HFD), followed by the oral delivery of PcP extracts. The results demonstrated that the administration of PcP extract effectively decreased dyslipidemia and hepatic steatosis, which coincided with a decrease in hepatic pyroptosis through modulation of the NLRP3/Caspase‐1/GSDMD pathway in liver tissues. Overall, our findings provide insight into the mechanism by which PcP extracts alleviate hepatic steatosis, highlighting the potential significance of modulating the NLRP3/Caspase‐1/GSDMD pathway in the context of pyroptosis.

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Protocatechuic acid relieves ferroptosis in hepatic lipotoxicity and steatosis via regulating NRF2 signaling pathway

Feng,

Shi,

Zhang

et al. 2024

Cell Biol Toxicol

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Ferroptosis represents a newly programmed cell death, and the process is usually accompanied with iron-dependent lipid peroxidation. Importantly, ferroptosis is implicated in a myriad of diseases. Recent literature suggests a potential position of ferroptosis in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD), the most widespread liver ailment worldwide. Intriguingly, several functional genes and metabolic pathways central to ferroptosis are regulated by nuclear factor erythroid-derived 2-like 2 (NRF2). In current work, we aim to identify protocatechuic acid (PCA), a primary metabolite of antioxidant polyphenols, as a potent NRF2 activator and ferroptosis inhibitor in the hepatic lipotoxicity and steatosis models. Herein, both NRF2 +/+ and NRF2 −/− cell lines and mice were used to analyze the importance of NRF2 in PCA function, and hepatic lipotoxicity and steatosis models were induced by palmitic acid and high-fat diet respectively. Our results indicated that ferroptosis was mitigated by PCA intervention in hepatic cells. Furthermore, PCA exhibited therapeutic efficacy against ferroptosis, as well as hepatic lipotoxicity and steatosis. The protective role of PCA was predominantly mediated through NRF2 activation, potentially elucidating a pivotal mechanism underlying PCA's therapeutic impact on MAFLD. Additionally, the augmented mitochondrial TCA cycle activity observed in hepatic lipotoxicity and steatosis models was ameliorated by PCA, in part via NRF2-dependent pathways, further bolstering PCA's anti-ferroptosis properties. Collectively, our findings underscore PCA’s potential in alleviating hepatic ferroptosis, lipotoxicity and steatosis via inducing activation of NRF2 signaling pathway, offering a promising strategy for the therapy of MAFLD as well as related lipid metabolic disorders. Supplementary Information The online version contains supplementary material available at 10.1007/s10565-024-09953-7.

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Mesenchymal stem cells alleviate palmitic acid-induced endothelial-to-mesenchymal transition by suppressing endoplasmic reticulum stress

Cited by 21 publications

References 33 publications

Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs

Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs

Penthorum chinense Pursh extract ameliorates hepatic steatosis by suppressing pyroptosis via the NLRP3/Caspase‐1/GSDMD pathway

Protocatechuic acid relieves ferroptosis in hepatic lipotoxicity and steatosis via regulating NRF2 signaling pathway

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