Increased alveolar soluble annexin V promotes lung inflammation and fibrosis

Buckley, Sue; Shi, Wei; Xu, Wei; Frey, Mark R.; Moats, Rex; Pardo, Annie; Selman, Moisés; Warburton, David

doi:10.1183/09031936.00002115

Cited by 16 publications

(8 citation statements)

References 42 publications

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“…These are a family of tyrosine kinase receptors, which include Her1 (epidermal growth factor receptor (EGFR)), Her2, Her3 and Her4. Several of these receptors have reported roles in epithelial remodeling, epithelial proliferation and are found to play significant roles in models of fibrosis 44 45 46 . Further dysfunction within this pathway is supported by the finding of enrichment within the downregulated proteome for EGFR (Her1) signaling.…”

Section: Discussionmentioning

confidence: 99%

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes

O’Dwyer

Norman

Xia

et al. 2017

Sci Rep

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

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Section: Discussionmentioning

confidence: 99%

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes

O’Dwyer

Norman

Xia

et al. 2017

Sci Rep

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“…Annexin 5 is an anticoagulant protein that acts as an indirect inhibitor of thromboplastin-specific complex and PLA2 [ 72 79 ]. Previous studies suggested an important roles for annexin 5 in the inflammation of tissues such as the heart, vascular endothelial cells, and lung, and in systemic sepsis [ 80 81 82 83 84 ]. Modifications in annexin 5 expression have been implicated in cardiovascular diseases [ 85 ], cancers [ 72 ], osteoarthritis [ 86 ], and rheumatoid arthritis [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

Time-dependent proteomic and genomic alterations in Toll-like receptor-4-activated human chondrocytes: increased expression of lamin A/C and annexins

Kim

Anh

et al. 2017

Korean J Physiol Pharmacol

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Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including ‘chemotaxis’, ‘hematopoietic organ development’, ‘positive regulation of cell proliferation’, and ‘regulation of cytokine biosynthetic process’. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

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“…These were tyrosine kinase receptor families, including Her1 (epidermal growth factor receptor (EGFR)), Her2, Her3, and Her4. Several of these receptors have been reported to play an important role in epithelial remodeling and epithelial hyperplasia, and have been found to play an important role in the brosis model [41][42][43]. EGFR (c-erbB1) played a key role in the maintenance and repair of epithelial tissue.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based mechanistic investigation of Jinshui Huanxian formula acing on idiopathic pulmonary fibrosis

Liu

et al. 2020

Preprint

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Background Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease with high incidence rate, morbidity and mortality. Jinshui Huanxian formula (JHF) is an empirical formula for the pathogenesis of lung-kidney qi deficiency and phlegm-blood stasis in pulmonary fibrosis. The purpose of this study is to explore the pharmacological mechanism of JHF action in IPF therapy by network interaction analysis. Methods The main active components and corresponding target genes of JHF were predicted using various databases. Two sets of IPF disease genes were obtained from the DisGeNET database and GEO database. Two sets of drug targets for IPF treatment were collected and the overlapping genes between disease genes and drug targets were analyzed. The target genes of JHF were intersected with the differentially expressed genes of IPF to obtain the predicted targets of JHF acting on IPF. The functions and pathways of predicted targets acting on IPF were analyzed by using DAVID and KEGG pathway database. Finally, the resulting drug target mechanisms were validated in a rat model of pulmonary fibrosis. Results 494 active compounds and 1304 corresponding targets were screened. Intersection analysis showed that 4 genes were common genes of JHF targets, IPF disease genes and anti-IPF drugs in KEGG database, and these genes were targeted by several compounds of JHF respectively. 72 JHF targets were closely related with IPF, and were thus considered therapeutically relevant. The targets were screened and participated in the regulation of IPF through 18 pathways. The molecular functions of targets included regulation of oxidoreductase activity, kinase regulator activity, phosphotransferase activity and transmembrane receptor protein kinase activity. In vivo experiments showed that JHF could alleviate the degree of pulmonary fibrosis, including the decrease of collagen deposition and epithelial-mesenchymal transition. Conclusions This study explored the mechanisms of JHF from a systematic point of view, trying to identify the specific target pathways acing on IPF. Pharmacological network with in vivo validation explained the potential roles and mechanisms of JHF in IPF therapy.

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Increased alveolar soluble annexin V promotes lung inflammation and fibrosis

Cited by 16 publications

References 42 publications

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes

Time-dependent proteomic and genomic alterations in Toll-like receptor-4-activated human chondrocytes: increased expression of lamin A/C and annexins

Network pharmacology-based mechanistic investigation of Jinshui Huanxian formula acing on idiopathic pulmonary fibrosis

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