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.

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 Monocyte-derived multipotent cell delivered programmed therapeutics to reverse idiopathic pulmonary fibrosis

2020 ◽  
Vol 6 (22) ◽  
pp. eaba3167 ◽  
Author(s):  
Xin Chang ◽  
Lei Xing ◽  
Yi Wang ◽  
Chen-Xi Yang ◽  
Yu-Jing He ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Targeted Delivery ◽  
Alveolar Epithelial Cell ◽  
Synergetic Effect ◽  
Engineered Nanoparticles ◽  
Matrix Metalloproteinase 2 ◽  
Alveolar Epithelial ◽  
The Matrix ◽  
Delivery Platform

Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous and fatal disease. However, IPF treatment has been limited by the low drug delivery efficiency to lungs and dysfunctional “injured” type II alveolar epithelial cell (AEC II). Here, we present surface-engineered nanoparticles (PER NPs) loading astaxanthin (AST) and trametinib (TRA) adhered to monocyte-derived multipotent cell (MOMC) forming programmed therapeutics (MOMC/PER). Specifically, the cell surface is designed to backpack plenty of PER NPs that reach directly to the lungs due to the homing characteristic of the MOMC and released PER NPs retarget injured AEC II after responding to the matrix metalloproteinase-2 (MMP-2) in IPF tissues. Then, released AST can enhance synergetic effect of TRA for inhibiting myofibroblast activation, and MOMC can also repair injured AEC II to promote damaged lung regeneration. Our findings provide proof of concept for developing a strategy for cell-mediated lung-targeted delivery platform carrying dual combined therapies to reverse IPF.

scholarly journals Right place, right time: the evolving role of herpesvirus infection as a “second hit” in idiopathic pulmonary fibrosis

2012 ◽  
Vol 302 (5) ◽  
pp. L441-L444 ◽  
Author(s):  
Jonathan A. Kropski ◽  
William E. Lawson ◽  
Timothy S. Blackwell
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Molecular Techniques ◽  
Alveolar Epithelial Cells ◽  
Herpesvirus Infection ◽  
Second Hit ◽  
Alveolar Epithelial

Over the course of the past decade, increasing evidence has implicated alveolar epithelial cell injury and dysfunction in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Genetic factors, cigarette smoking, and other environmental exposures have been identified as potential factors leading to a population of vulnerable alveolar epithelial cells. In addition, molecular techniques have demonstrated herpesviruses are commonly detectable in the lungs of patients with IPF, raising suspicion that, in the setting of a vulnerable alveolar epithelium, lytic (or latent) herpesvirus infection may act as a “second hit” leading to the development of pulmonary fibrosis. Intriguingly, in vivo modeling has shown that herpesvirus infection induces or worsens lung fibrosis when combined with immunodeficiency or other injurious stimuli. Here, we discuss potential mechanisms through which herpesvirus infection may contribute to the pathogenesis of IPF. Ultimately, antiviral therapy may hold promise for halting the progression of this deadly disease.

scholarly journals Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence

2020 ◽  
Vol 11 ◽  
Author(s):  
Li Zhang ◽  
Xiang Tong ◽  
Jizhen Huang ◽  
Man Wu ◽  
Shijie Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Cell Senescence ◽  
Alveolar Epithelial Cells ◽  
Inflammatory Factors ◽  
Collagen Deposition ◽  
Alveolar Epithelial ◽  
Compound C

Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharmacological functions. However, the role of FIS in pulmonary fibrosis has not been established. In this study, we found that FIS treatment apparently alleviated BLM-induced weight loss, inflammatory cells infiltration, inflammatory factors expression, collagen deposition and alveolar epithelial cell senescence, along with AMPK activation and the down regulation of NF-κB and TGF-β/Smad3 in vivo. In vitro, FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-β/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. FIS may be a promising candidate for patients with pulmonary fibrosis.

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