Knockdown of LSD1 meliorates Ox-LDL-stimulated NLRP3 activation and inflammation by promoting autophagy via SESN2-mesiated PI3K/Akt/mTOR signaling pathway

Zhuo, Xianlu; Wu, Yan; Yang, Yanjie; Gao, Li; Qiao, Xiangrui; Chen, Tao

doi:10.1016/j.lfs.2019.116696

Cited by 35 publications

(25 citation statements)

References 40 publications

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“…Shi et al reported that LSD1 dowm-regulates autophagy of myoblast cells via the activity the mTOR signaling pathway [46]. A recent study has revealed that knockdown of LSD1 attenuates ox-LDL-induced in ammation of RAW264.7 cells by promoting mTORmediated autophagy [47]. In this study, we found that knockdown of LSD1 suppressed IL-1β-induced chondrocyte apoptosis, in ammation and ECM degradation by activating mTOR-mediated autophagy.…”

Section: Discussionsupporting

confidence: 56%

Knockdown of LSD1 alleviates the IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy

Wei

Liu

et al. 2021

Preprint

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Osteoarthritis (OA) is a common joint disease with characteristics of chronic inflammation and articular cartilage degeneration. It has been proved that LSD1 was up-regulated in OA cartilage tissues, but its role and regulatory mechanism in OA are unclear. Herein, interleukin 1 beta (IL-1β)-treated human chondrocytes was performed as a cell model of OA. Then, LSD1 expression was found that up-regulated in OA cartilage tissues and IL-1β-induced chondrocytes. Knockdown of LSD1 increased cell viability, while decreased apoptosis rate and inflammatory cytokines secretion levels in IL-1β-induced chondrocytes. In addition, knockdown of LSD1 reduced the expression of catabolic proteins (MMP-13 and ADAMTS-5) and enhanced the expression of anabolic proteins (Collagen II and Aggrecan) in chondrocytes after IL-1β stimulation. Moreover, overexpression of TRIM32 repressed chondrocyte viability, while promoted IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation. The expression of LSD1 and TRIM32 in OA cartilage was positively correlated, and knockdown of LSD1 down-regulated TRIM32 expression of chondrocytes. Our data further indicated that LSD1 regulated autophagy of chondrocytes through modulating TRIM32. Overexpression of TRIM32 reduced the effect of LSD1 knockdown on IL-1β-induced chondrocytes, while activating autophagy by Rapamycin further reversed this reduction. Therefore, our study shows that knockdown of LSD1 inhibited IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy.

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Section: Discussionsupporting

confidence: 56%

Knockdown of LSD1 alleviates the IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy

Wei

Liu

et al. 2021

Preprint

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“…The PI3K/Akt/mTOR signaling pathway has been demonstrated that it plays an important role in regulating autophagy in AS ( Jiang et al, 2017 ) and our study has shown that ox-LDL could activate this pathway ( Zhuo et al, 2019 ). Propofol reduces cell adhesion by inhibiting Cx43 and the downstream PI3K/Akt/NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 71%

Inhibition of Connexin 43 reverses ox-LDL-mediated inhibition of autophagy in VSMC by inhibiting the PI3K/Akt/mTOR signaling pathway

Qin

Yang

et al. 2022

PeerJ

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Background Oxidized low-density lipoproteins (ox-LDL) may induce foam cell formation from the vascular smooth muscle cell (VSMC) by inhibiting VSMC autophagy. This process accelerates the formation of atherosclerosis (AS). Connexin 43 (Cx43), which is the most widely distributed connexin in VSMC is associated with autophagy. However, the mechanism of action and the involvement of Cx43 in ox-LDL-inhibited VSMC autophagy remain unclear. Methods The primary VSMC were obtained and identified, before primary VSMC were pretreated with an inhibitor (Cx43-specific inhibitor Gap26 and PI3K inhibitor LY294002) and stimulated with ox-LDL. Results Ox-LDL not only inhibited autophagy in VSMC via downregulation of autophagy-related proteins (such as Beclin 1, LC3B, p62), but also increased Cx43 protein levels. Then we added Gap26 to VSMC in the ox-LDL+Gap26 group, in which autophagy-related proteins were increased and the accumulation of lipid droplets was reduced. These result suggested that an enhanced level of autophagy and an alleviation of lipid accumulation might be caused by inhibiting Cx43 in VSMC. The phosphorylation levels of PI3K, AKT, mTOR were increased by ox-LDL, thus down-regulating autophagy-related proteins. However, this situation was partially reversed by the Gap26. Moreover, Cx43 expression were decreased by LY294002 in ox-LDL-induced VSMCs. Conclusion Inhibiting Cx43 may activate VSMC autophagy to inhibit foam cell formation by inhibiting the PI3K/AKT/mTOR signaling pathway.

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“…Activation of several signaling pathways including AKT/mTOR signaling, can promote NLRP3 inflammasome activation and EMT process. For instance, studies have shown that AKT/mTOR pathway can regulate NLRP3 activation and inflammation (41). And, the AKT/ mTOR signaling is also essential for EMT, which eventually contributes to the pathobiology of fibrosis (42).…”

Section: A B Cmentioning

confidence: 99%

Andrographolide alleviates bleomycin-induced NLRP3 inflammasome activation and epithelial-mesenchymal transition in lung epithelial cells by suppressing AKT/mTOR signaling pathway

Li¹,

Yang²,

Yang³

et al. 2021

Ann Transl Med

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Background: Andrographolide (Andro), a diterpenoid extracted from Andrographis paniculata, has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear.This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells. Methods:The in vivo effects of Andro were evaluated in a rat model of BLM-induced pulmonary fibrosis.The roles of Andro in BLM-induced NLRP3 inflammasome activation, EMT and AKT/mTOR signaling were investigated using human alveolar epithelial A549 cells.Results: We found that Andro significantly alleviated pulmonary edema and histopathological changes, decreased weight loss, and reduced collagen deposition. Andro downregulated the levels of NLRP3, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in the lungs of BLM-treated rats, suggesting the inhibitory effect of Andro on NLRP3 inflammasome activation in vivo. Additionally, the symptoms of BLM-mediated EMT phenotype in the lung were also attenuated after Andro administration. In vitro, Andro also markedly inhibited BLM-induced NLRP3 inflammasome activation and EMT in A549 cells. Moreover, Andro inhibited BLM-induced phosphorylation of AKT and mTOR in A549 cells, suggesting that AKT/mTOR inactivation mediates Andro-induced effects on BLMinduced NLRP3 inflammasome activation and EMT.Conclusions: These data indicate that Andro can reduce BLM-induced pulmonary fibrosis through suppressing NLRP3 inflammasome activation and EMT in lung epithelial cells via AKT/mTOR signaling pathway.

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Knockdown of LSD1 meliorates Ox-LDL-stimulated NLRP3 activation and inflammation by promoting autophagy via SESN2-mesiated PI3K/Akt/mTOR signaling pathway

Cited by 35 publications

References 40 publications

Knockdown of LSD1 alleviates the IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy

Knockdown of LSD1 alleviates the IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy

Inhibition of Connexin 43 reverses ox-LDL-mediated inhibition of autophagy in VSMC by inhibiting the PI3K/Akt/mTOR signaling pathway

Andrographolide alleviates bleomycin-induced NLRP3 inflammasome activation and epithelial-mesenchymal transition in lung epithelial cells by suppressing AKT/mTOR signaling pathway

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