scholarly journals Role of various imbalances centered on alveolar epithelial cell/fibroblast apoptosis imbalance in the pathogenesis of idiopathic pulmonary fibrosis

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Qing Wang ◽  
Zhao-Liang Xie ◽  
Qi Wu ◽  
Zhi-Xian Jin ◽  
Chao Yang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial

scholarly journals Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

2014 ◽  
Vol 306 (5) ◽  
pp. L405-L419 ◽  
Author(s):  
Saaket Varma ◽  
Poornima Mahavadi ◽  
Satish Sasikumar ◽  
Leah Cushing ◽  
Tessa Hyland ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mouse Models ◽  
Human Lung ◽  
Alveolar Epithelial Cell ◽  
Lung Epithelium ◽  
Chronic Injury ◽  
Alveolar Epithelial

Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity.

Involvement of Alveolar Epithelial Cell Necroptosis in Idiopathic Pulmonary Fibrosis Pathogenesis

2018 ◽  
Vol 59 (2) ◽  
pp. 215-224 ◽  
Author(s):  
Ji-Min Lee ◽  
Masahiro Yoshida ◽  
Mi-So Kim ◽  
June-Hyuk Lee ◽  
Ae-Rin Baek ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial

scholarly journals Molecular biomarkers in idiopathic pulmonary fibrosis

2014 ◽  
Vol 307 (9) ◽  
pp. L681-L691 ◽  
Author(s):  
Brett Ley ◽  
Kevin K. Brown ◽  
Harold R. Collard
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Underlying Disease ◽  
Current Approach ◽  
Molecular Biomarkers ◽  
Alveolar Epithelial ◽  
Cell Dysfunction ◽  
Collaborative Efforts ◽  
Intended Use

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF.

Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Benjamin J. Moss ◽  
Stefan W. Ryter ◽  
Ivan O. Rosas
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Alveolar Epithelial Cell ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Metabolic Dysfunction ◽  
Epithelial Repair

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves a complex interplay of cell types and signaling pathways. Recurrent alveolar epithelial cell (AEC) injury may occur in the context of predisposing factors (e.g., genetic, environmental, epigenetic, immunologic, and gerontologic), leading to metabolic dysfunction, senescence, aberrant epithelial cell activation, and dysregulated epithelial repair. The dysregulated epithelial cell interacts with mesenchymal, immune, and endothelial cells via multiple signaling mechanisms to trigger fibroblast and myofibroblast activation. Recent single-cell RNA sequencing studies of IPF lungs support the epithelial injury model. These studies have uncovered a novel type of AEC with characteristics of an aberrant basal cell, which may disrupt normal epithelial repair and propagate a profibrotic phenotype. Here, we review the pathogenesis of IPF in the context of novel bioinformatics tools as strategies to discover pathways of disease, cell-specific mechanisms, and cell-cell interactions that propagate the profibrotic niche. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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