Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

Sun, Wei; Jing, Xiaoyan; Yang, Xiaoyu; Huang, Hui; Luo, Qun; Xia, Shu; Wang, Ping; Wang, Na; Zhang, Qian; Guo, Jian; Xu, Zuojun

doi:10.18632/aging.203335

Cited by 23 publications

(8 citation statements)

References 37 publications

(41 reference statements)

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“…Under pathological conditions, ATs release IGF1, which activates the surface of adjacent normal ATs. IGF receptor (IGFR-1), and further activate the PI3K/AKT signaling pathway, and participate in ATs senescence and IPF by releasing CTGF, TGF-β1 and MMP9 ( Sun et al, 2021 ).…”

Section: Cells and Regulatorsmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

et al. 2022

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Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.

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Section: Cells and Regulatorsmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

et al. 2022

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“…However, subtype S2 also showed decreased gene enrichment in blood vessel development and the PI3K-Akt signaling pathway, which contradicts this speculation. Blood vessel development is an important component of interstitial lung disease (Ackermann et al, 2020) and the PI3K-Akt pathway contributes to pulmonary fibrosis (Sun et al, 2021). In the immune cell infiltration analysis, the abundance of Th2 and Th17 cells did not differ between the two subtypes.…”

Section: Discussionmentioning

confidence: 92%

Predictive investigation of idiopathic pulmonary fibrosis subtypes based on cellular senescence-related genes for disease treatment and management

et al. 2023

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Background: Idiopathic pulmonary fibrosis (IPF), a chronic, progressive lung disease characterized by interstitial remodeling and tissue destruction, affects people worldwide and places a great burden on society. Cellular senescence is thought to be involved in the mechanisms and development of IPF. The aim of this study was to predictively investigate subtypes of IPF according to cellular senescence-related genes and their correlation with the outcome of patients with IPF, providing possible treatment and management options for disease control.Methods: Gene expression profiles and follow-up data were obtained from the GEO database. Senescence-related genes were obtained from the CSGene database and analyzed their correlation with the outcome of IPF. A consensus cluster was constructed to classify the samples based on correlated genes. The GSVA and WGCNA packages in R were used to calculate the immune-related enriched fractions and construct gene expression modules, respectively. Metascape and the clusterProfiler package in R were used to enrich gene functions. The ConnectivityMap was used to probe suitable drugs for potential treatment.Results: A total of 99 cellular senescence-related genes were associated with IPF prognosis. Patients with IPF were divided into two subtypes with significant prognostic differences. Subtype S2 was characterized by enhanced fibrotic progression and infection, leading to acute exacerbation of IPF and poor prognosis. Finally, five cellular senescence-related genes, TYMS, HJURP, UBE2C, BIRC5, and KIF2C, were identified as potential biomarkers in poor prognostic patients with IPF.Conclusion: The study findings indicate that cellular senescence-related genes can be used to distinguish the prognosis of patients with IPF. Among them, five genes can be used as candidate biomarkers to predict patients with a poor prognostic subtype for which anti-fibrosis and anti-infection treatments could be suitable.

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“…34 In addition, recent studies suggest a critical link between the IGF Article ll OPEN ACCESS system and pulmonary fibrosis. 35 We and others have previously highlighted the crucial role of IGFBP5 in the pathogenesis of IPF. 36,37 Present study findings demonstrate suppressed levels of IGFBP2 expression in AEC2 cells both in aged mice and in humans with lung fibrosis.…”

Section: Discussionmentioning

confidence: 95%