Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease

Wu, Yanjun; Xu, Bo; He, Xin; Wu, Bo; Li, Yunxiao; Yu, Ganggang; Tan, Che-Kim; Wang, Haoyan

doi:10.3892/mmr.2018.8831

Cited by 12 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GD and FD patients exhibit chronic inflammation and elevated level of pro-inflammatory cytokines in blood [3, 47–49], and it is unclear how chronic inflammation impacts SQSTM1/p62 level. For example, patients with chronic obstructive pulmonary disease (COPD) with increased levels of Il-6, Il-8, TNF-α demonstrated decreased levels of SQSTM1/p62 in PBMCs [50]. Our RT-PCR study demonstrated reduced mRNA level of SQSTM1/p62 in GD1 and FD PBMCs.…”

Section: Discussionmentioning

confidence: 74%

Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases

et al. 2019

View full text Add to dashboard Cite

The major cellular clearance pathway for organelle and unwanted proteins is the autophagy-lysosome pathway (ALP). Lysosomes not only house proteolytic enzymes, but also traffic organelles, sense nutrients, and repair mitochondria. Mitophagy is initiated by damaged mitochondria, which is ultimately degraded by the ALP to compensate for ATP loss. While both systems are dynamic and respond to continuous cellular stressors, most studies are derived from animal models or cell based systems, which do not provide complete real time data about cellular processes involved in the progression of lysosomal storage diseases in patients. Gaucher and Fabry diseases are rare sphingolipid disorders due to the deficiency of the lysosomal enzymes; glucocerebrosidase and α-galactosidase A with resultant lysosomal dysfunction. Little is known about ALP pathology and mitochondrial function in patients with Gaucher and Fabry diseases, and the effects of enzyme replacement therapy (ERT). Studying blood mononuclear cells (PBMCs) from patients, we provide in vivo evidence, that regulation of ALP is defective. In PBMCs derived from Gaucher patients, we report a decreased number of autophagic vacuoles with increased cytoplasmic localization of LC3A/B, accompanied by lysosome accumulation. For both Gaucher and Fabry diseases, the level of the autophagy marker, Beclin1, was elevated and ubiquitin binding protein, SQSTM1/p62, was decreased. mTOR inhibition did not activate autophagy and led to ATP inhibition in PBMCs. Lysosomal abnormalities, independent of the type of the accumulated substrate suppress not only autophagy, but also mitochondrial function and mTOR signaling pathways. ERT partially restored ALP function, LC3-II accumulation and decreased LC3-I/LC3-II ratios. Levels of lysosomal (LAMP1), autophagy (LC3), and mitochondrial markers, (Tfam), normalized after ERT infusion. In conclusion, there is mTOR pathway dysfunction in sphingolipidoses, as observed in both PBMCs derived from patients with Gaucher and Fabry diseases, which leads to impaired autophagy and mitochondrial stress. ERT partially improves ALP function.

show abstract

Section: Discussionmentioning

confidence: 74%

Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases

et al. 2019

View full text Add to dashboard Cite

show abstract

“…14 Another evidence suggested that autophagy can promote the release of inflammatory cytokines, which contributes to the inflammatory response of COPD. 15 However, extensive validations are needed to improve the understanding of autophagy in pathogenesis of COPD.…”

Section: Discussionmentioning

confidence: 99%

“…17 Moreover, one previous study demonstrated that autophagy-associated protein levels of PBMCs in COPD patients were increased and were correlated with FEV 1 % predicted values and circulating levels of cytokines. 15 However, there are still few related studies in this field, and further investigations will be required to better understand this field.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Autophagy-Related Genes in Chronic Obstructive Pulmonary Disease

Sun¹,

Shen²,

Wang³

et al. 2021

COPD

View full text Add to dashboard Cite

Autophagy plays essential roles in the development of COPD. We aim to identify and validate the potential autophagy-related genes of COPD through bioinformatics analysis and experiment validation. Methods: The mRNA expression profile dataset GSE38974 was obtained from GEO database. The potential differentially expressed autophagy-related genes of COPD were screened by R software. Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed autophagy-related genes. Finally, RNA expression of top five differentially expressed autophagy-related genes was validated in blood samples from COPD patients and healthy controls by qRT-PCR. Results: A total of 40 differentially expressed autophagy-related genes (14 up-regulated genes and 26 down-regulated genes) were identified between 23 COPD patients and 9 healthy controls. The PPI results demonstrated that these autophagy-related genes interacted with each other. The GO and KEGG enrichment analysis of differentially expressed autophagy-related genes indicated several enriched terms related to autophagy and mitophagy. The results of qRT-PCR showed that the expression levels of HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 in COPD patients and healthy controls were consistent with the bioinformatics analysis results from mRNA microarray. Conclusion: We identified 40 potential autophagy-related genes of COPD through bioinformatics analysis. HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 may affect the development of COPD by regulating autophagy. These results may expand our understanding of COPD and might be useful in the treatment of COPD.

show abstract

“… 4 It can degrade damaged and degenerated macromolecules and organelles in the cytoplasm. 5 The degradation products can be recycled, providing the raw materials for normal cellular survival and metabolism. 5 However, excessive autophagy will induce excess cell damage, resulting in programmed cell death.…”

Section: Introductionmentioning

confidence: 99%

The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter

Zhang

Wang

et al. 2020

J Int Med Res

View full text Add to dashboard Cite

Objective Many lung diseases are associated with changes in autophagic activity. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a key regulatory role in autophagy. Our aim was to explore the function of PI3K/AKT/mTOR pathway on autophagy in chronic obstructive pulmonary disease (COPD) caused by particulate matter with a diameter <2.5 µm (PM2.5). Methods Male C57BL/6 mice were randomly divided into sham, model, and PI3K inhibitor groups. Mice were exposed to PM2.5 for 4 weeks to establish an in vivo COPD model. Alveolar epithelial cells were stimulated with PM2.5 to establish an in vitro COPD model. Results In mice with COPD induced by PM2.5, the PI3K inhibitor PF-04979064 suppressed protein expression of PI3K, p-AKT, and p-mTOR to increase apoptosis of alveolar epithelial cells and reduce autophagy. Short interfering PI3K suppressed the PI3K/AKT/mTOR pathway to induce apoptosis and reduce autophagy of alveolar epithelial cells in an in vitro model of COPD. Activation of PI3K induced the PI3K/AKT/mTOR pathway to reduce apoptosis of alveolar epithelial cells in the in vitro model of COPD by promoting autophagy. Conclusions These data demonstrate that PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in COPD.

show abstract

Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease

Cited by 12 publications

References 42 publications

Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases

Impaired autophagic and mitochondrial functions are partially restored by ERT in Gaucher and Fabry diseases

Identification and Validation of Autophagy-Related Genes in Chronic Obstructive Pulmonary Disease

The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter

Contact Info

Product

Resources

About