Stimulatory effect of gastroesophageal reflux disease (GERD) on pulmonary fibroblast differentiation

Chiang, Cheng Che; Chen, Chin‐Ming; Suen, Jau‐Ling; Su, Hsiang Han; Hsieh, Chong Chao; Cheng, C. C.

doi:10.1016/j.dld.2020.07.010

Cited by 5 publications

(5 citation statements)

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“…For example, the FGFR2b ligand can inhibit lung fibrosis and promote tissue repair and regeneration ( Dorry et al, 2020 ). GERD has been shown to increase the expression of FGFs and promote the differentiation of lung fibroblasts, mediate the upregulation of α-SMA, and activate RhoA/ROCK signaling to participate in IPF( Huang et al, 2010 ; Chiang et al, 2020 ). Additionally, GERD, arising from neurotrophin expression disorders and inflammation in the esophageal smooth muscle, triggers neuronal abnormalities and impaired esophageal motility ( Chen et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

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Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Wu,

Xiao,

Fang

et al. 2024

Front. Pharmacol.

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Background: The etiological underpinnings of gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) remain elusive, coupled with a scarcity of effective therapeutic interventions for IPF. Angelicae sinensis radix (ASR, also named Danggui) is a Chinese herb with potential anti-fibrotic properties, that holds promise as a therapeutic agent for IPF.Objective: This study seeks to elucidate the causal interplay and potential mechanisms underlying the coexistence of GERD and IPF. Furthermore, it aims to investigate the regulatory effect of ASR on this complex relationship.Methods: A two-sample Mendelian randomization (TSMR) approach was employed to delineate the causal connection between gastroesophageal reflux disease and IPF, with Phennoscanner V2 employed to mitigate confounding factors. Utilizing single nucleotide polymorphism (SNPs) and publicly available microarray data, we analyzed potential targets and mechanisms related to IPF in GERD. Network pharmacology and molecular docking were employed to explore the targets and efficacy of ASR in treating GERD-related IPF. External datasets were subsequently utilized to identify potential diagnostic biomarkers for GERD-related IPF.Results: The IVW analysis demonstrated a positive causal relationship between GERD and IPF (IVW: OR = 1.002, 95%CI: 1.001, 1.003; p < 0.001). Twenty-five shared differentially expressed genes (DEGs) were identified. GO functional analysis revealed enrichment in neural, cellular, and brain development processes, concentrated in chromosomes and plasma membranes, with protein binding and activation involvement. KEGG analysis unveiled enrichment in proteoglycan, ERBB, and neuroactive ligand-receptor interaction pathways in cancer. Protein-protein interaction (PPI) analysis identified seven hub genes. Network pharmacology analysis demonstrated that 104 components of ASR targeted five hub genes (PDE4B, DRD2, ERBB4, ESR1, GRM8), with molecular docking confirming their excellent binding efficiency. GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF (ESR1: AUCGERD = 0.762, AUCIPF = 0.725; GRM8: AUCGERD = 0.717, AUCIPF = 0.908). GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF, validated in external datasets.Conclusion: This study establishes a causal link between GERD and IPF, identifying five key targets and two potential diagnostic biomarkers for GERD-related IPF. ASR exhibits intervention efficacy and favorable binding characteristics, positioning it as a promising candidate for treating GERD-related IPF. The potential regulatory mechanisms may involve cell responses to fibroblast growth factor stimulation and steroidal hormone-mediated signaling pathways.

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Section: Discussionmentioning

confidence: 99%

“…In addition, several studies ( Lee et al, 2018 ) have found that lung fibroblasts can be transformed into neurons under certain conditions to participate in tissue repair. The differentiation-stimulating effect of GERD on lung-resident cells ( Chiang et al, 2020 ) may be related to this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Wu,

Xiao,

Fang

et al. 2024

Front. Pharmacol.

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“…Gastroesophageal reflux disease (GERD) is one of the most predominant gastrointestinal diseases with a prevalence in the US between 18.1-27.8% and 8.8-25.9% in Europe (an even higher incidence is to be assumed due to an availability of over-the-counter anti-acidic medication) [39,40]. Studies suggest that cell damage and inflammation caused by gastric fluid may trigger the wound healing process and subsequent immunomodulation, promoted by inflammatory cytokines and chemokine activation [41]. Inflammatory cytokines cause fibroblast to myofibroblast transition, leading to fibrosis [42].…”

Section: Discussionmentioning

confidence: 99%

Distinguishing Benign and Malignant Findings on [68 Ga]-FAPI PET/CT Based on Quantitative SUV Measurements

et al. 2022

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Aim/Purpose Fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts. However, activated fibroblasts have been shown to play a significant role also in certain benign conditions such as wound healing or chronic inflammation. Therefore, the current study aimed to identify whether FAPI uptake might differ between malignant lesions and benign conditions. Material and Methods We retrospectively analyzed 155 patients with various cancer types who received [68 Ga]-FAPI-04/02-PET/CT between July 2017 and March 2020. SUVmax, SUVmean, and lesion-to-background ratios (LBR) of FAPI uptake were measured in benign processes compared to malignant lesions (primary and/or 2 exemplary metastases). In addition, receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive capabilities of semiquantitative PET/CT parameters. Furthermore, the sensitivity, specificity, optimal cutoff value, and 95% confidence interval (CI) were determined for each parameter. Results Benign lesions exhibited significantly lower FAPI uptake compared to malignant lesions (mean SUVmax benign vs. malignant: 4.2 vs. 10.6; p < 0.001). In ROC analysis, cutoff values of these lesions (benign vs. malignant) were established based on SUVmax, SUVmean, and LBR. The SUVmax cutoff value for all lesions was 5.5 and the corresponding sensitivity, specificity, accuracy, and AUC were 78.8%, 85.1%, 82.0%, and 0.89%, respectively. Conclusion Our aim was to systematically analyze the pattern of FAPI uptake in benign and malignant processes. This investigation demonstrates that FAPI uptake might be useful to differentiate malignant and benign findings due to different patho-physiological origins.

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“…Others such as obstructive sleep apnoea (OSA) causing repetitive nocturnal hypoxaemia may be important contributors to the development and/or progression of fibrotic lung disease. [108][109][110] Targeted treatment of conditions may be considered, even where specific evidence may be lacking, for the indication of improving IPF-specific outcomes and quality of life. classification scheme, (precapillary PH associated with lung diseases and/or hypoxia).…”

Section: Treatment and Impact Of Co-morbiditiesmentioning

confidence: 99%

“…Some conditions including lung cancer, chronic obstructive pulmonary disease (COPD)/emphysema and coronary artery disease are highly prevalent in patients with IPF due to the shared risk of tobacco exposure. Others such as obstructive sleep apnoea (OSA) causing repetitive nocturnal hypoxaemia may be important contributors to the development and/or progression of fibrotic lung disease 108–110 . Targeted treatment of conditions may be considered, even where specific evidence may be lacking, for the indication of improving IPF‐specific outcomes and quality of life.…”

Section: Pharmacological Therapymentioning

confidence: 99%

Treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis: A position statement from the Thoracic Society of Australia and New Zealand 2023 revision

Mackintosh,

Keir,

Troy

et al. 2024

Respirology

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Idiopathic pulmonary fibrosis (IPF) is a progressive disease leading to significant morbidity and mortality. In 2017 the Thoracic Society of Australia and New Zealand (TSANZ) and Lung Foundation Australia (LFA) published a position statement on the treatment of IPF. Since that time, subsidized anti‐fibrotic therapy in the form of pirfenidone and nintedanib is now available in both Australia and New Zealand. More recently, evidence has been published in support of nintedanib for non‐IPF progressive pulmonary fibrosis (PPF). Additionally, there have been numerous publications relating to the non‐pharmacologic management of IPF and PPF. This 2023 update to the position statement for treatment of IPF summarizes developments since 2017 and reaffirms the importance of a multi‐faceted approach to the management of IPF and progressive pulmonary fibrosis.

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Stimulatory effect of gastroesophageal reflux disease (GERD) on pulmonary fibroblast differentiation

Cited by 5 publications

References 47 publications

Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Distinguishing Benign and Malignant Findings on [68 Ga]-FAPI PET/CT Based on Quantitative SUV Measurements

Treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis: A position statement from the Thoracic Society of Australia and New Zealand 2023 revision

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