Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

Ma, Huili; Wu, Xuyi; Li, Yang; Xia, Yong

doi:10.3389/fphar.2022.963054

Cited by 30 publications

(29 citation statements)

References 273 publications

(263 reference statements)

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“…IPF is the most common form of chronic interstitial pneumonia. Although its etiology is unknown, imbalance of apoptosis of alveolar epithelial cells or fibroblasts is one of the important pathogenic mechanisms ( Ma et al, 2022b ). TGF-β enhanced the expression of DOCK2 and the FMT marker α-SMA in primary human lung fibroblast (HLF), and DOCK2 knockdown also dramatically attenuated the TGF-β-induced expression of the FMT marker.…”

Section: Role Of Dock2 In Diseasesmentioning

confidence: 99%

Insights from DOCK2 in cell function and pathophysiology

Luo

et al. 2022

Front. Mol. Biosci.

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Dedicator of cytokinesis 2 (DOCK2) can activate the downstream small G protein Rac and regulate cytoskeletal reorganization. DOCK2 is essential for critical physiological processes such as migration, activation, proliferation, and effects of immune cells, including lymphocytes, neutrophils, macrophages, and dendritic cells. For example, DOCK2 is involved in the development and activation of T and B lymphocytes by affecting synapse formation and inhibiting the development of the Th2 lineage by downregulating IL-4Rα surface expression. Not only that, DOCK2 may be a molecular target for controlling cardiac transplant rejection and Alzheimer’s disease (AD). Patients with defects in the DOCK2 gene also exhibit a variety of impaired cellular functions, such as chemotactic responses of lymphocytes and reactive oxygen species (ROS) production by neutrophils. To date, DOCK2 has been shown to be involved in the development of various diseases, including AD, pneumonia, myocarditis, colitis, tumors, etc. DOCK2 plays different roles in these diseases and the degree of inflammatory response has a different impact on the progression of disease. In this paper, we present a review of recent advances in the function of DOCK2 in various immune cells and its role in various diseases.

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Section: Role Of Dock2 In Diseasesmentioning

confidence: 99%

Insights from DOCK2 in cell function and pathophysiology

Luo

et al. 2022

Front. Mol. Biosci.

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“…Evaluation of chest computed tomography (CT) supports the early diagnosis of ILDs [ 4 , 5 ]. Recent studies have identified the key role of crosstalk among dysregulated epithelial cells, mesenchymal cells, immune cells, endothelial cells, genetic mutations and environmental factors (e.g., smoking) in idiopathic pulmonary fibrosis, a subtype of IIP [ 6 ]. Patients with IIPs occasionally have clinical features suggesting the presence of autoimmune diseases, including positive autoantibodies, without meeting the diagnostic criteria for any CTD.…”

Section: Introductionmentioning

confidence: 99%

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias

et al. 2022

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Various autoantibodies are associated with clinical outcomes in patients with idiopathic interstitial pneumonias (IIPs). We retrospectively analyzed the association between autoantibodies and malignancies in IIP patients. Comprehensive analyses of autoantibodies were performed using immunoprecipitation and enzyme-linked immunosorbent assays in 193 consecutive IIP patients. Cancer-related factors were analyzed using logistic regression analysis. In total, 22 of 193 patients (11.4%) with IIP had malignant disease. In univariate analysis, positivity for any autoantibody (odds ratio (OR), 3.1; 95% confidence interval (CI), 1.2–7.7; p = 0.017) and antinuclear antibody titer ≥ 1:320 (OR, 3.4; CI, 1.2–9.8; p = 0.024) were significantly associated with malignancies. Positive anti-aminoacyl tRNA synthetase (ARS) (OR, 3.7; CI, 0.88–15.5; p = 0.074) and anti-Ro52 antibody (OR, 3.2; CI, 0.93–11.2; p = 0.065) tended to be associated with malignancies. In multivariate analysis, independent risk factors were male sex (OR, 3.7; CI, 1.0–13.5; p = 0.029) and positivity for any autoantibody (OR, 3.9; CI, 1.5–10.1; p = 0.004) in model 1, and male sex (OR, 3.9; CI, 1.0–15.3; p = 0.049), antinuclear antibody titer ≥1:320 (OR, 4.2; CI, 1.4–13.3; p = 0.013), and positivity for anti-ARS antibody (OR, 6.5; CI, 1.2–34.1; p = 0.026) in model 2. Positivity for any autoantibody, antinuclear and anti-ARS antibodies, and male sex were independent risk factors for malignancies in IIP patients. Testing autoantibodies in IIP patients might help the early diagnosis of malignancies.

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“…Idiopathic pulmonary fibrosis (IPF), which primarily affects older male smokers, is the paradigm of chronic progressive idiopathic fibrosis. It is characterized with a histopathological and radiological point of view by the usual interstitial pneumonia (UIP) pattern [ 1 , 2 ]. IPF’s natural course is unpredictable and the pathophysiological mechanisms underlying the disease, the anatomical remodeling and progression, are currently under investigation [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…More relevant, accurate biomarkers to prognosticate and guide management for patients affected by this disease are still needed. Current paradigms into IPF pathogenesis, a disease as lethal as malignant disorders, hypothesize altered apoptosis mechanisms as well as changes in cellular and intracellular pathways [ 1 , 2 ]. Epithelial damage, fibroblasts activation and proliferation, cell senescence, and aberrant immunological responses were all considered as relevant in this complex scenario [ 2 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis

Vitis¹,

D’Ascanio

Sacconi³

et al. 2022

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a disease characterized by progressive scarring of the lung that involves the pulmonary interstitium. The disease may rapidly progress, leading to respiratory failure, and the long-term survival is poor. There are no accurate biomarkers available so far. Our aim was to evaluate the expression of the B4GALT1 in patients with IPF. Analysis of B4GALT1 gene expression was performed in silico on two gene sets, retrieved from the Gene Expression Omnibus database. Expression of B4GALT1 was then evaluated, both at the mRNA and protein levels, on lung specimens obtained from lung biopsies of 4 IPF patients, on one IPF-derived human primary cell and on 11 cases of IPF associated with cancer. In silico re-analysis demonstrated that the B4GALT1 gene was overexpressed in patients and human cell cultures with IPF (p = 0.03). Network analysis demonstrated that B4GALT1 upregulation was correlated with genes belonging to the EMT pathway (p = 0.01). The overexpression of B4GALT1 was observed, both at mRNA and protein levels, in lung biopsies of our four IPF patients and in the IPF-derived human primary cell, in other fibrotic non-lung tissues, and in IPF associated with cancer. In conclusion, our results indicate that B4GALT1 is overexpressed in IPF and could represent a novel marker of this disease.

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Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

Cited by 30 publications

References 273 publications

Insights from DOCK2 in cell function and pathophysiology

Insights from DOCK2 in cell function and pathophysiology

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias

B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis

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