LKB1/p53/TIGAR/autophagy-dependent VEGF expression contributes to PM2.5-induced pulmonary inflammatory responses

Xu, Huan; Xu, Xiuduan; Wang, Hongli; Qimuge, Aodeng; Li, Shasha; Chen, Yuanlian; Zhang, Chongchong; Hu, Meiru; Song, Lun

doi:10.1038/s41598-019-53247-6

Cited by 24 publications

(19 citation statements)

References 37 publications

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“…Recently, some studies have shown that autophagy, as an important mechanism that maintains the dynamic balance of the cell microenvironment and cell self-renewal, is involved in the progression of respiratory diseases caused by PM2.5. 17 , 59 , 60 During acute pulmonary inflammation, activation of autophagy appears to be a protective mechanism for the host to respond to bacterial and viral infections. 61 Meanwhile, regulating autophagy has also become a potential mechanism to alleviate PM2.5-induced lung injury.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Pei¹,

Wang²,

Huang³

et al. 2021

JIR

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Introduction Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells). Methods The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells. Results After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro. Conclusion Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.

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Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Pei¹,

Wang²,

Huang³

et al. 2021

JIR

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“…The result was not statistically significant, which indicates that lncGm16410 may not act as a cis -acting gene. Recent studies have shown that exposure to particulate pollutants in the environment can lead to the activation of SRC protein-mediated signaling pathways, which in turn might trigger autophagy and inflammatory responses ( Xu et al, 2016 , Xu et al, 2019 ). To further investigate the changes in SRC protein expression in response to PM 2 .…”

Section: Resultsmentioning

confidence: 99%

lncRNA Gm16410 Mediates PM2.5-Induced Macrophage Activation via PI3K/AKT Pathway

et al. 2021

Front. Cell Dev. Biol.

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PM2.5 refers to atmospheric particulate matters with a diameter of less than 2.5 μm. The deposit of PM2.5 in lung cells can cause oxidative stress, leading to changes in macrophage polarity, which can subsequently cause pulmonary inflammation. Long-chain non-coding RNA (lncRNA) is a class of transcripts that regulate biological processes through multiple mechanisms. However, the role of lncRNA in PM2.5-induced lung inflammation has not been established. In this study, the biological effects and associated mechanism of lncRNA in PM2.5-induced change in macrophage polarity were investigated. The lncRNA-mediated PM2.5-induced macrophage inflammation and lung inflammation-associated injury were also determined. Mice were exposed to chronic levels of PM2.5, and changes in the expression of lncRNA in the lung were measured by lncRNA microarray. lncRNAs that showed significant changes in expression in response to PM2.5 were identified. lncRNA showing the biggest change was subjected to further analysis to determine its functional roles and mechanisms with respect to macrophage activation. The result showed that a significant reduction in expression of one lncRNA, identified as lncGm16410, was observed in the lung of mice and RAW264.7 cells following exposure to PM2.5. lncGm16410 suppressed PM2.5-induced macrophage activation via the SRC protein-mediated PI3K/AKT signaling pathway. PM2.5 promoted lung inflammation by downregulating the expression of lncGm16410, enhancing the activation of macrophages. Thus, lncGm16410 might provide new insight into the prevention of PM2.5 injury.

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“…The process of type II programmed cell death, namely autophagy, is closely implicated in the pathophysiology of non-small-cell lung cancer as well as the pathogenesis of many other pulmonary diseases, which contributes to protein degradation and cell apoptosis [23,24]. Studies have corroborated elevated autophagy level in PM2.5-induced lung injury and pulmonary inflammatory responses [12,25]. Increased autophagy level was also detected in our study in PM2.5-treated BEAS-2B cells, which is consistent with previous studies.…”

Section: Discussionmentioning

confidence: 98%

REDD1 (regulated in development and DNA damage-1)/autophagy inhibition ameliorates fine particulate matter (PM2.5) -induced inflammation and apoptosis in BEAS-2B cells

Li¹,

Xu²,

Wang

et al. 2021

Bioengineered

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This study aimed to investigate the implication of REDD1 on airborne particle matter-induced lung injury and whether it is mediated through autophagy. Cell viability in BEAS-2B cells induced by PM2.5 was measured by CCK-8. RT-qPCR and Western blot were performed to determine mRNA and protein levels of REDD1 as well as inflammatory cytokines, respectively. Cell apoptosis was observed with TUNEL staining. The expression of autophagy-related genes was detected by Western blot. Autophagy level was observed with GFP-LC3 staining. PM2.5 induced the expression of REDD1 in BEAS-2B cells. The inhibition by silencing REDD1 ameliorated the viability damage, blocked the inflammatory response and reduced the number of apoptotic BEAS-2B cells all induced by PM2.5. It was also found that PM2.5 induced autophagy in BEAS-2B cells, which was reversed by interference with REDD1. Furthermore, interference with REDD1 alleviated PM2.5-induced cell damage, inflammatory response and apoptosis in BEAS-2B cells through inhibiting autophagy. REDD1/autophagy inhibition ameliorates PM2.5-induced viability damage, inflammation and apoptosis in BEAS-2B cells.

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LKB1/p53/TIGAR/autophagy-dependent VEGF expression contributes to PM2.5-induced pulmonary inflammatory responses

Cited by 24 publications

References 37 publications

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

lncRNA Gm16410 Mediates PM2.5-Induced Macrophage Activation via PI3K/AKT Pathway

REDD1 (regulated in development and DNA damage-1)/autophagy inhibition ameliorates fine particulate matter (PM2.5) -induced inflammation and apoptosis in BEAS-2B cells

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