B and T lymphocyte attenuator regulates autophagy in mycobacterial infection via the AKT/mTOR signal pathway

Liu, Jiao; Ming, Siqi; Shi, Weifeng; Meng, Xiangjun; Xiao, Qiang; Wu, Minhao; Wu, Yongjian; Xie, Hanbin; Zhou, Jie; Zhong, Haibo; Huang, Xi

doi:10.1016/j.intimp.2020.107215

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…The mTOR signal pathway can be activated by various external factors such as growth factors, stress, oxygen, and amino acid, and is involved in many physiological processes, such as liposome synthesis, energy metabolism, and autophagy. The inducible knockout of mTOR in mouse airway epithelial cells and alveolar type II epithelial cells will exacerbate smoking-induced inflammation, autophagy, necrosis, and apoptosis, which will lead to airway inflammation and emphysema ( Liu et al, 2021 ; Wu et al, 2021 ; Ye et al, 2021 ). MircoRNA-mRNA regulatory network in Figure 3C demonstrated that KPNA6 and TOR1AIP2 were targeted by four miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Huang

Zhang

et al. 2022

Front. Genet.

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This study aims to use bioinformatics methods to determine the epigenetic changes in microRNA expression and DNA methylation caused by cigarette smoking. The data of mRNA, miRNA expression, and methylation microarray were obtained from the GEO database to filter differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and methylated CpG probes (DMPs) through the limma package. The R clusterProfile package was used for functional annotation and enrichment analysis. The protein-protein interaction (PPI) network was constructed by the String database and visualized in Cytoscape software. Starbase database was employed to predict lncRNA and CirRNA based on the sequence of miRNA, and to establish a regulatory network of ceRNA. By overlapping DEG and DEM, 107 down-miRNA-targeted up-regulated genes and 65 up-miRNA-target down-regulated genes were obtained, which were mainly enriched in autophagy signaling pathways and protein ubiquitination pathways, respectively. In addition, 324 genes with low methylation and high expression and 204 genes with high methylation and low expression were respectively related to the degeneration of the nervous system and the function of the cardiovascular system. Interestingly, 43 genes were up-regulated under the dual regulation of reduced miRNA and hypomethylation, while 14 genes were down-regulated under the dual regulation of increased miRNA and hypermethylation. Ten chemicals have been identified as putative therapeutic agents for pathological conditions caused by smoking. In addition, among these genes, HSPA4, GRB2, PRKCA, and BCL2L1 could play a fundamental role in related diseases caused by smoking and may be used as the biomarkers for precise diagnosis and targets for future therapies of smoking-related diseases.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Huang

Zhang

et al. 2022

Front. Genet.

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“…However, the dynamics of autophagy activity under basal conditions and upon infection as well as and its impact on mycobacterial viability over time is largely under-studied. Most M. tb studies have either explored this process using a limited number of autophagy markers [ 3 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] or studying one time point only [ 3 , 38 , 39 , 40 , 41 , 42 , 45 , 46 ]. The present study focused on documenting autophagy induction and turnover in different infection conditions over time, also using different analytical tools.…”

Section: Discussionmentioning

confidence: 99%

“…It has recently been shown that p62 levels respond rapidly to autophagy induction [ 32 , 33 , 34 , 35 ]. In M. tb infection, studies either use one autophagy marker [ 3 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] to track this process or several markers at a single time point [ 3 , 38 , 39 , 40 , 41 , 42 , 45 , 46 ] to investigate the autophagy induction capability of their protein/treatment of interest. These approaches do however have their limitations.…”

Section: Introductionmentioning

confidence: 99%

Measurement of Autophagy Activity Reveals Time-Dependent, Bacteria-Specific Turnover during Mycobacterium tuberculosis Infection

et al. 2022

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The intracellular pathogen, Mycobacterium tuberculosis (M. tb) uses various mechanisms to evade its killing. One of such is phagosomal damage and cytosolic translocation which is then targeted by the host’s bactericidal autophagy pathway. It is suggested that cytosolic translocation of M. tb is time-dependent, occurring at later time points of 48 to 72 h post-infection. It is, however, not known whether increased autophagic targeting correlates with these time points of infection. We investigated the time-dependent profile of autophagy activity through the course of M. tb infection in mammalian macrophages. Autophagy activity was inferred by the turnover measurement of autophagy markers and M. tb bacilli in THP-1 and RAW 264.7 macrophages. Over a period of 4 to 72 h, we observed highest autophagy turnover at 48 h of infection in M. tb-containing cells. This was evident by the highest turnover levels of p62 and intracellular M. tb. This supports observations of phagosomal damage mostly occurring at this time point and reveal the correlation of increased autophagy activity. The findings support the preservation of autophagy activity despite M. tb infection while also highlighting time-dependent differences in M. tb-infected macrophages. Future studies may explore time-dependent exogenous autophagy targeting towards host-directed anti-tuberculosis therapy.

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“…Evidences have shown that MAPK, such as Erk1/2, JNK and p38 MAPK, and Akt signalling pathways are involved in various aspects of cellular physiology, including inflammation, apoptosis, and autophagy [15][16][17][18]. Several pathogens participate in autophagy through the MAPK or Akt signalling pathways [17,[19][20][21][22]. To preliminarily explore the relationship between autophagy induced by M. hyopneumoniae and the corresponding signalling pathways, we evaluated the phosphorylation of Erk1/2, JNK, p38, and Akt in AH-infected 3D4/21 cells at different time points.…”

Section: Hyopneumoniae Induces Autophagy Via the Jnk And Akt Signalli...mentioning

confidence: 99%

Incomplete autophagy promotes the proliferation of Mycoplasma hyopneumoniae through the JNK and Akt pathways in porcine alveolar macrophages

Wen

Chen

Tian

et al. 2022

Vet Res

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Autophagy is an important conserved homeostatic process related to nutrient and energy deficiency and organelle damage in diverse eukaryotic cells and has been reported to play an important role in cellular responses to pathogens and bacterial replication. The respiratory bacterium Mycoplasma hyopneumoniae has been identified to enter porcine alveolar macrophages, which are considered important immune cells. However, little is known about the role of autophagy in the pathogenesis of M. hyopneumoniae infection of porcine alveolar macrophages. Our experiments demonstrated that M. hyopneumoniae infection enhanced the formation of autophagosomes in porcine alveolar macrophages but prevented the fusion of autophagosomes with lysosomes, thereby blocking autophagic flux and preventing the acidification and destruction of M. hyopneumoniae in low-pH surroundings. In addition, using different autophagy regulators to intervene in the autophagy process, we found that incomplete autophagy promoted the intracellular proliferation of M. hyopneumoniae. We also found that blocking the phosphorylation of JNK and Akt downregulated the autophagy induced by M. hyopneumoniae, but pathways related to two mitogen-activated protein kinases (Erk1/2 and p38) did not affect the process. Collectively, M. hyopneumoniae induced incomplete autophagy in porcine alveolar macrophages through the JNK and Akt signalling pathways; conversely, incomplete autophagy prevented M. hyopneumoniae from entering and degrading lysosomes to realize the proliferation of M. hyopneumoniae in porcine alveolar macrophages. These findings raise the possibility that targeting the autophagic pathway may be effective for the prevention or treatment of M. hyopneumoniae infection.

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B and T lymphocyte attenuator regulates autophagy in mycobacterial infection via the AKT/mTOR signal pathway

Cited by 12 publications

References 43 publications

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

Measurement of Autophagy Activity Reveals Time-Dependent, Bacteria-Specific Turnover during Mycobacterium tuberculosis Infection

Incomplete autophagy promotes the proliferation of Mycoplasma hyopneumoniae through the JNK and Akt pathways in porcine alveolar macrophages

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