EGFR Signaling in Lung Fibrosis

Schramm, Fabian; Schaefer, Liliana; Wygrecka, Małgorzata

doi:10.3390/cells11060986

Cited by 29 publications

(22 citation statements)

References 109 publications

(146 reference statements)

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“…On the basis of these findings, we speculate that ZBM can also exert antipulmonary fibrosis effects through the JAK/STAT signaling axis. Interestingly, the epidermal growth factor receptor (EGFR), a member of the ErbB tyrosine kinase receptor family, was shown to participate in wound healing and tissue regeneration by activating downstream PI3K/AKT, MAPK/ERK, and STAT signaling pathways [ 66 ]. In our study, we found that ZBM also significantly modulated the expression of EGFR and SRC, a nonreceptor tyrosine kinase that activates STAT3 and trans-activates EGFR.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis Strategy Based on Network Pharmacology to Investigate the Potential Mechanism of Fritillaria thunbergii Miq. against Idiopathic Pulmonary Fibrosis

Feng

Sun

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Idiopathic pulmonary fibrosis (IPF) is a long-term, distressing, and age-related interstitial lung disease characterized by a complicated etiology and irreversible progression. Fritillaria thunbergii Miq. (Zhe Beimu, ZBM) is frequently used for its heat-clearing and phlegm-resolving properties in herbal compounds for the treatment of IPF. However, the specific mechanisms underlying the effects of ZBM against IPF have not yet been reported. In this study, we applied a systematic analysis strategy based on network pharmacology to explore the probable core targets and major pathways of ZBM against IPF. In addition, molecular docking simulation and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to preliminarily investigate the possible mechanisms underlying the therapeutic effects of ZBM on IPF. We collected a total of 86 components of ZBM and used network pharmacology analysis to screen nine presumptive targets of ZBM against IPF. The molecular-docking results indicated that the components of ZBM exhibited good binding activity with presumptive targets. The qRT-PCR results also suggested that ZBM may partly alleviate IPF by regulating the expression of presumptive targets. This study laid the foundation for further clinical applications of ZBM and the development of IPF-related therapeutic products.

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Section: Discussionmentioning

confidence: 99%

Systematic Analysis Strategy Based on Network Pharmacology to Investigate the Potential Mechanism of Fritillaria thunbergii Miq. against Idiopathic Pulmonary Fibrosis

Feng

Sun

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…6, F and G). Given the evidence for aberrant EGFR signaling in lung fibrosis (50-52) and the differential expression of both EGFR receptors and ligands in the cluster B cells, the sensitivity of cluster B cells to EGFR inhibitors may provide a cellular mechanism for the efficacy of such drugs in model systems (51)(52)(53)(54)(55)(56).…”

Section: Ipf Stem Cell Variants In Small-molecule Screensmentioning

confidence: 99%

Cloning a profibrotic stem cell variant in idiopathic pulmonary fibrosis

et al. 2023

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Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of lung alveoli with dense fibrotic matrices. Although the mechanisms initiating IPF remain unclear, rare and common alleles of genes expressed in lung epithelia, combined with aging, contribute to the risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified lung basal cell heterogeneity in IPF that might be pathogenic. We used single-cell cloning technologies to generate “libraries” of basal stem cells from the distal lungs of 16 patients with IPF and 10 controls. We identified a major stem cell variant that was distinguished from normal stem cells by its ability to transform normal lung fibroblasts into pathogenic myofibroblasts in vitro and to activate and recruit myofibroblasts in clonal xenografts. This profibrotic stem cell variant, which was shown to preexist in low quantities in normal and even fetal lungs, expressed a broad network of genes implicated in organ fibrosis and showed overlap in gene expression with abnormal epithelial signatures identified in previously published scRNA-seq studies of IPF. Drug screens highlighted specific vulnerabilities of this profibrotic variant to inhibitors of epidermal growth factor and mammalian target of rapamycin signaling as prospective therapeutic targets. This profibrotic stem cell variant in IPF was distinct from recently identified profibrotic stem cell variants in chronic obstructive pulmonary disease and may extend the notion that inappropriate accrual of minor and preexisting stem cell variants contributes to chronic lung conditions.

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“…The contribution of airway epithelial cells to the development of IPF is supported by multiple lines of evidence, including the cellular composition and morphological alterations of IPF airways, strong associations between the MUC5B promoter rs35705950 polymorphism and the risk of IPF, and the bronchiolization of distal airspaces in IPF lungs. The contribution of airway epithelial cells to IPF pathogenesis is also addressed by Schramm et al, who discuss the role of the ErbB receptor–ligand system in lung fibrosis [ 15 ]. Intriguingly, the deregulation of the ErbB receptor-ligand axis is mainly observed in the regions of alveolar bronchiolization.…”

mentioning

confidence: 99%

“…This underlies the pivotal role of ErbB receptors in the reprogramming of airway epithelial cells, and thereby honeycomb cyst formation and IPF progression. The authors of this comprehensive review emphasize the dual role of ErbB receptors and their ligands in lung fibrosis and indicate the need to elaborately characterize the dynamics and causal flows in the ErbB signaling networks in acute versus chronic lung injury [ 15 ].…”

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confidence: 99%