Study of the common activating mechanism of apoptosis and epithelial-to-mesenchymal transition in alveolar type II epithelial cells

Wang, Jiali; Xue, Tianjiao; Ye, Huan; Sang, Chen; Wu, Shuai; Li, Shanshan

doi:10.1016/j.resp.2020.103584

Cited by 10 publications

(7 citation statements)

References 30 publications

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“…It was concluded that the Jagged1-Notch interaction induces endothelial-to-mesenchymal transformation (17). Another experiment on the epithelial mesenchymal transformation of pulmonary fibrosis type II alveolar epithelial cells found that, compared with the control group, the alveoli in the experimental group shrank, collapsed, and fused, the alveolar septum was significantly widened, and a large number of inflammatory cells infiltrated the pulmonary stroma (18). In vivo and in vitro studies of the experimental group showed that the expression of Zo-1 and VE-Cadherin decreased, accompanied by the increased expression of Notch-1, NICD, HES-1, and twist-1, while the expression of VE-Cadherin and Zo-1 increased significantly after treatment with Notch-1 siRNA (18).…”

Section: Discussionmentioning

confidence: 99%

“…This study observed that the fluorescence intensity of the Notch overexpression group was significantly lower than that of the Model control group, while the fluorescence intensity of VE-Cadherin and Zo-1 protein in the low-expression group was higher than that of the Model group, suggesting that Notch signal expression significantly inhibited the expression of VE-Cadherin and Zo-1 protein during ALI, thereby increasing the permeability of pulmonary capillary barrier. However, a study (18) found that atypical Notch signals mediated by blood flow can promote barrier integrity. Blood laminar shear stress promotes the expression of Notch ligand DLL4 and the cleavage of Notch receptor.…”

Section: Discussionmentioning

confidence: 99%

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Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Yang,

Ma,

et al. 2023

Braz J Med Biol Res

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This study focused on the effect and mechanism of Notch signal on pulmonary microvascular endothelial cells (PMVECs) following acute lung injury. PMVECs were cultured in vitro and randomly divided into eight groups. Grouping was based on whether cells were co-cultured with T cells (splenic CD4 + T cells were isolated using MACS microbeads) and the level of Notch expression: Normal group and Normal+T cells group, Model group and Model+T cells group, Notch low-expression group and Notch low-expression+T cells group, and Notch overexpression group and Notch overexpression+T cells group. Except for the Normal group and Normal+T cells group, all other groups were treated with 500 mL lipopolysaccharide (1 mg/mL). The expression of VE-cadherin and Zo-1 protein in the Model group (with or without T cells) was lower than that in the normal group (with or without T cells), their expression in the Notch low-expression group (with or without T cells) was significantly increased, and their expression in the Notch overexpression group (with or without T cells) was significantly decreased. Compared with the normal+T cells group, the number of Treg cells in the Notch low-expression+T cells group decreased significantly (Po0.01). The number of Th17 cells in the Notch overexpression+T cells group was higher than that in the Model+T cells group (Po0.01), while the number of Treg cells decreased (Po0.01). Our results demonstrated that activated Notch signal can down-regulate the expression of the tight junction proteins VE-Cadherin and Zo-1 in PMVECs and affect Th17/Treg immune imbalance. Autophagy was discovered to be involved in this process.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Yang,

Ma,

et al. 2023

Braz J Med Biol Res

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“…Little is known about the function of AI-2 in modulating the behaviors of the host. Pyocyanin, which is a virulence factor of P. aeruginosa , can increase TGF-β1 secretion (Wang et al, 2021 ), while elastase, which is another virulence factor of P. aeruginosa , can increase IL-6 secretion (Li et al, 2021 ). Both TGF-β and IL-6 are crucial cytokines in the differentiation of CD4+ T cells into Th17 cells.…”

Section: Discussionmentioning

confidence: 99%

Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway

et al. 2022

Front. Microbiol.

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Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that causes various acute and chronic lung infections in immunocompromised patients. We previously found that a quorum sensing (QS) signal, namely, autoinducer-2 (AI-2), facilitates the pathogenicity of the wild-type (WT) P. aeruginosa PAO1 strain in vitro and in vivo. However, the immunological mechanism that leads to pulmonary injury remains to be elucidated. In this study, we aimed to investigate the effects of AI-2 on interleukin-17A (IL-17A) production during acute P. aeruginosa PAO1 lung infection using a mouse model, with an emphasis on the underlying immunological mechanism. Compared to infection with P. aeruginosa PAO1 alone, infection with P. aeruginosa PAO1 combined with AI-2 treatment resulted in significantly increased levels of IL-17A, numbers of Th17 cells and levels of STAT3 in the lung tissues of WT mice (P < 0.05), as well as more serious lung damage. In contrast, the concentrations of the proinflammatory cytokines IL-1α, IL-1β, and IL-6 and the chemokine keratinocyte-derived chemokine (KC) were significantly reduced during P. aeruginosa lung infection in IL-17A−/− mice compared with WT mice (P < 0.05), and no effects were observed after AI-2 treatment (P > 0.05). Furthermore, the level of IL-17A in the lungs of WT mice was significantly reduced following infection with a P. aeruginosa strain harboring mutations in the QS genes lasR and rhlR compared with the level of IL-17A following infection with P. aeruginosa PAO1. Our data suggest that AI-2 promotes P. aeruginosa PAO1 acute lung infection via the IL-17A pathway by interfering with the QS systems of P. aeruginosa. IL-17A may be a therapeutic target for the treatment of acute P. aeruginosa lung infections in the clinic.

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“…Pulmonary brosis caused by mesenchymal transformation after alveolar epithelial cells are damaged is the main mechanism leading to lung function impairment [22,23] . Clinically, when patients with compromised immunity are infected with pseudomonas aeruginosa, pyocyanin can stimulate cells to show oxidative stress, and then activate TGF-β1/smad signaling pathway to induce EMT in cells and aggravate pulmonary brosis [19,20,24] .…”

Section: Autophagy May Affect Emt Through Tgf-β/smad Signaling Pathwaymentioning

confidence: 99%

Effect of autophagy on EMT in alveolar epithelial cells induced by pyocyanin

Li,

Wang,

2024

Preprint

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Objective Epithelial-Mesenchymal Transition (EMT) plays an important role in the occurrence and development of pulmonary fibrosis, which can cause severe cell damage. Autophagy is a process of maintaining cell balance through degradation and reuse of damaged organelles, proteins, invading pathogens and other substances. Autophagy can protect cells to a certain extent, while uncontrolled and defective autophagy will further aggravate cell damage. At present, it has been reported that autophagy can reduce the level of apoptosis and mesenchymal transformation caused by certain pathogenic factors. Therefore, the aim of this study was to investigate the effect of autophagy on EMT in alveolar type II epithelial cells stimulated by pyocyanin (PCN). Methods After stimulating human alveolar type II epithelial cell line A549 with different concentrations of PCN in vitro, EMT changes were detected by Western blot and Real-time PCR, and autophagy levels were detected by immunofluorescence and Western blot. Then autophagy was inhibited and EMT marker protein levels and nucleic acid levels were detected. Finally, the changes of TGF-β/Smad pathway markers were detected after the addition of autophagy inhibitor 3-MA. Result After stimulating A549 cells with PCN (5ug/ml, 10ug/ml, 25ug/ml, 50ug/ml) for 24h, The expression levels of epithelial marker E-cadherin protein and mRNA were significantly decreased compared with the control group, and the expression levels of mesenchymal marker α-SMA protein and mRNA were increased compared with the control group (p < 0.05), suggesting that EMT phenomenon occurred after PCN stimulated A549 cells. At the same time, the expression of autophagy marker LC3 in protein level and immunofluorescence level was significantly higher than that in control group (p < 0.05), suggesting that PCN induced autophagy in A549 cells. After inhibition of autophagy with 3MA, the protein and nucleic acid expression levels of autophagy marker LC3 and epithelial marker E-cadherin were significantly decreased compared with control group, while the protein and nucleic acid expression levels of mesenchymal marker α-SMA were increased compared with control group (p < 0.05), indicating that the EMT phenomenon was enhanced after inhibition of autophagy. Further study showed that TGF-β1 nucleic acid level and p-Smad2/3 protein expression level in the addition of autophagy inhibitor 3MA group were significantly increased compared with the control group and PCN group (p < 0.05), indicating that inhibition of autophagy may enhance EMT by affecting TGF-β/Smad pathway. Conclusion PCN can induce EMT and autophagy in alveolar epithelial cells, and autophagy can inhibit the further development of EMT, which may inhibit the occurrence of EMT by reducing the activity of TGF-β/Smad pathway. These results suggest that autophagy may prevent pulmonary fibrosis.

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Study of the common activating mechanism of apoptosis and epithelial-to-mesenchymal transition in alveolar type II epithelial cells

Cited by 10 publications

References 30 publications

Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Autoinducer-2 promotes Pseudomonas aeruginosa PAO1 acute lung infection via the IL-17A pathway

Effect of autophagy on EMT in alveolar epithelial cells induced by pyocyanin

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