Oxidative/nitrosative stress, autophagy and apoptosis as therapeutic targets of melatonin in idiopathic pulmonary fibrosis

2018 ◽  
Vol 22 (12) ◽  
pp. 1049-1061 ◽  
Author(s):  
Azam Hosseinzadeh ◽  
Seyed Ali Javad-Moosavi ◽  
Russel J. Reiter ◽  
Rasoul Yarahmadi ◽  
Habib Ghaznavi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Nitrosative Stress ◽  
Therapeutic Targets

scholarly journals Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets

2018 ◽  
Vol 71-72 ◽  
pp. 112-127 ◽  
Author(s):  
Justin C. Hewlett ◽  
Jonathan A. Kropski ◽  
Timothy S. Blackwell
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Targets

scholarly journals Peroxiredoxin II Expression and Its Association With Oxidative Stress and Cell Proliferation in Human Idiopathic Pulmonary Fibrosis

2008 ◽  
Vol 56 (10) ◽  
pp. 951-959 ◽  
Author(s):  
Kirsi Vuorinen ◽  
Steffen Ohlmeier ◽  
Outi Leppäranta ◽  
Kaisa Salmenkivi ◽  
Marjukka Myllärniemi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Nitrosative Stress ◽  
Usual Interstitial Pneumonia ◽  
Normal Lung ◽  
Proliferating Cells ◽  
Two Dimensional Gel Electrophoresis ◽  
Western Blots ◽  
Lung Biopsies

Oxidant burden has been suggested to be a contributor to the pathogenesis of idiopathic pulmonary fibrosis (IPF). The study focused on peroxiredoxin (Prx) II, an antioxidant that has been associated with platelet-derived growth factor (PDGF) signaling and consequent cell proliferation. Localization and expression of Prx II, PDGF receptors (PDGFRα, PDGFRβ), Ki67, and nitrotyrosine were assessed in control ( n = 10) and IPF/usual interstitial pneumonia (UIP) ( n = 10) lung biopsies by immunohistochemistry and morphometry. Prx II oxidation was determined by standard and non-reducing Western blots, two-dimensional gel electrophoresis, and mass spectrometry. Prx II localized in the IPF/UIP epithelium and alveolar macrophages. Prx II–positive area in the fibroblastic foci (FF) was smaller than in other parenchymal areas ( p = 0.03) or in the hyperplastic epithelium ( p = 0.01). There was no major Prx II oxidation in IPF/UIP compared with the normal lung. The FF showed only minor immunoreactivity to the PDGFRs; Ki67, a marker of cell proliferation; and nitrotyrosine, a marker of oxidative/nitrosative stress. The results suggest that Prx II oxidation does not relate to the pathogenesis of IPF/UIP and that Prx II, PDGFRs, and proliferating cells colocalize in the IPF/UIP lung. Unexpectedly, FF represented areas of low cell proliferation.

scholarly journals Therapeutic targets in idiopathic pulmonary fibrosis

2017 ◽  
Vol 131 ◽  
pp. 49-57 ◽  
Author(s):  
Martin Kolb ◽  
Francesco Bonella ◽  
Lutz Wollin
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Targets

scholarly journals Identification of Targetable Kinases in Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Hisao Higo ◽  
Kadoaki Ohashi ◽  
Shuta Tomida ◽  
Sachi Okawa ◽  
Hiromasa Yamamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Therapeutic Targets ◽  
Integrated Analysis ◽  
Potential Candidate ◽  
Tissue Samples ◽  
Kinase Expression

Abstract Background: Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF).Methods: Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n=13) and control samples (n=8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC).Results: Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions.Conclusions: We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. DCLK1 and STK33 can serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK may serve as personalized therapeutic targets of IPF.

scholarly journals Myriad Functions of Stanniocalcin-1 (STC1) Cover Multiple Therapeutic Targets in the Complicated Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF)

2015 ◽  
Vol 9s1 ◽  
pp. CCRPM.S23285 ◽  
Author(s):  
Shinya Ohkouchi ◽  
Manabu Ono ◽  
Makoto Kobayashi ◽  
Taizou Hirano ◽  
Yutaka Tojo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Aerobic Glycolysis ◽  
Therapeutic Targets ◽  
Vascular Leakage ◽  
Single Drug ◽  
The Status ◽  
Endothelial Homeostasis ◽  
Temporal And Spatial Heterogeneity

Idiopathic pulmonary fibrosis (IPF) is an intractable disease for which the pathological findings are characterized by temporal and spatial heterogeneity. The pathogenesis is composed of myriad factors, including repetitive injuries to epithelial cells, alterations in immunity, the formation of vascular leakage and coagulation, abnormal wound healing, fibrogenesis, and collagen accumulation. Therefore, the molecular target drugs that are used or attempted for treatment or clinical trials may not cover the myriad therapeutic targets of IPF. In addition, the complicated pathogenesis results in a lack of informative biomarkers to diagnose accurately the status of IPF. These facts point out the necessity of using a combination of drugs, that is, each single drug with molecular targets or a single drug with multiple therapeutic targets. In this review, we introduce a humoral factor, stanniocalcin-1 (STC1), which has myriad functions, including the maintenance of calcium homeostasis, the promotion of early wound healing, uncoupling respiration (aerobic glycolysis), reepithelialization in damaged tissues, the inhibition of vascular leakage, and the regulation of macrophage functions to keep epithelial and endothelial homeostasis, which may adequately cover the myriad therapeutic targets of IPF.

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