scholarly journals Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marina R. Hadjicharalambous ◽  
Benoit T. Roux ◽  
Eszter Csomor ◽  
Carol A. Feghali-Bostwick ◽  
Lynne A. Murray ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Human Lung ◽  
Lung Fibroblast ◽  
Human Lung Fibroblast ◽  
Non Coding Rnas

scholarly journals Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs

2020 ◽  
Vol 21 (2) ◽  
pp. 524 ◽  
Author(s):  
Marina R. Hadjicharalambous ◽  
Mark A. Lindsay
Keyword(s):  
Chronic Disease ◽  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Lung Fibroblast ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Non Coding Rnas

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as the secretion of fibrotic and inflammatory mediators, have been strongly associated with the development and progression of IPF. Significantly, long non-coding RNAs (lncRNAs) are emerging as modulators of multiple biological processes, although their function and mechanism of action in IPF is poorly understood. LncRNAs have been shown to be important regulators of several diseases and their aberrant expression has been linked to the pathophysiology of fibrosis including IPF. This review will provide an overview of this emerging role of lncRNAs in the development of IPF.

scholarly journals Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity

2000 ◽  
Vol 9 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Masahiro Sasaki ◽  
Masayuki Kashima ◽  
Takefumi Ito ◽  
Akiko Watanabe ◽  
Masaaki Sano ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Human Lung ◽  
Heparan Sulphate ◽  
Inhibitory Effect ◽  
Lung Fibroblast ◽  
Chemotactic Response ◽  
Fibroblast Proliferation ◽  
Human Lung Fibroblast ◽  
Fibroblast Migration

Fibroblast migration, proliferation, extacellular matrix protein synthesis and degradation are the key events in various biological and pathological processes in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients with plumomary fibrosis show increased numbers of mast cells which have metachromatic granules containing heparin, histamin and proteases. Little is known about how these products influence pulmonary fibrosis. In the present study, we investigated the effect of heparin and related glycosaminoglycans on PDGF-induced lung fibroblast proliferation and chemotactic responsein vitro. In addition, we examined the effect of heparin on both the induction of matorix metalloproteinases (MMPs) and MMPs activity in lung fibroblastsin vitro.Heparin, de-N-sulphated heparin but not heparan sulphate inhibited PDGF-induced lung fibroblast proliferation. In contrast, only heparin inhibited PDGF-stimulated human lung fibroblast chemotaxis. Negatively charged poly-L-gultamic acid had no effect on either fibroblast proliferation or chemotaxis. Thus the negative charge alone cannot account for the ant-proliferative and anti-chemotactic effects of heparin.Furthermore, heparin and heparan sulphate also had no inhibitory effect on induction of MMPs, including MMP-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP-9 (gelatinase B). Only heparin inhibited both MMP-1 and MMP-2/MMP-9 activity. Additionally, tissue inhibitor of metalloproteinase type 1 (TIMP-1) and type 2 (TIMP-2) inhibited PDGF-stimulated human lung fibroblast chemotaxis. The ability of heparin to inhibit fibroblast chemotaxis may account for the inhibitory effect of heparin on MMP activity.The above results suggested that heparin and related glycosaminoglycans differentially regulate PDGF-induced lung fibroblast proliferation, chemotaxis and MMPs activity and further that these effects may have a key role in extracellular matrix remodeling in inflammatory lung disease.

scholarly journals Reconstruction of the miR-506-Quaking axis in Idiopathic Pulmonary Fibrosis using integrative multi-source bioinformatics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stevan D. Stojanović ◽  
Maximilian Fuchs ◽  
Chunguang Liang ◽  
Kevin Schmidt ◽  
Ke Xiao ◽  
...  
Keyword(s):  
Data Mining ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Rna Sequencing ◽  
In Silico ◽  
Rna Binding ◽  
Human Lung ◽  
Model Systems ◽  
Lung Fibroblasts ◽  
Sequencing Analysis

AbstractThe family of RNA-binding proteins (RBP) functions as a crucial regulator of multiple biological processes and diseases. However, RBP function in the clinical setting of idiopathic pulmonary fibrosis (IPF) is still unknown. We developed a practical in silico screening approach for the characterization of RBPs using multi-sources data information and comparative molecular network bioinformatics followed by wet-lab validation studies. Data mining of bulk RNA-Sequencing data of tissues of patients with IPF identified Quaking (QKI) as a significant downregulated RBP. Cell-type specific expression was confirmed by single-cell RNA-Sequencing analysis of IPF patient data. We systematically analyzed the molecular interaction network around QKI and its functional interplay with microRNAs (miRs) in human lung fibroblasts and discovered a novel regulatory miR-506-QKI axis contributing to the pathogenesis of IPF. The in silico results were validated by in-house experiments applying model systems of miR and lung biology. This study supports an understanding of the intrinsic molecular mechanisms of IPF regulated by the miR-506-QKI axis. Initially applied to human lung disease, the herein presented integrative in silico data mining approach can be adapted to other disease entities, underlining its practical relevance in RBP research.

Effects of silica on human lung fibroblast in culture

2001 ◽  
Vol 270 (1-3) ◽  
pp. 135-139 ◽  
Author(s):  
G Arcangeli ◽  
V Cupelli ◽  
G Giuliano
Keyword(s):  
Human Lung ◽  
Lung Fibroblast ◽  
Human Lung Fibroblast

Surfactant downregulates synthesis of DNA and inflammatory mediators in normal human lung fibroblasts

1996 ◽  
Vol 270 (1) ◽  
pp. L159-L163 ◽  
Author(s):  
M. J. Thomassen ◽  
J. M. Antal ◽  
B. P. Barna ◽  
L. T. Divis ◽  
D. P. Meeker ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Human Lung ◽  
Thymidine Incorporation ◽  
Interleukin 1 ◽  
S Phase ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblast ◽  
Normal Human

The initial inflammatory event in the adult respiratory distress syndrome (ARDS) is followed by fibroproliferation and a cascade of fibroblast-derived mediators. Because lung fibroblasts may be exposed to surfactant as well as inflammatory cytokines during ARDS, we hypothesized that surfactant might modulate fibroblast activity. We previously demonstrated that surfactant inhibited production of inflammatory cytokines from endotoxin-stimulated human alveolar macrophages. In the current study the effects of surfactant on normal human lung fibroblast proliferative capacity and mediator production were examined. Both synthetic (Exosurf) and natural (Survanta) surfactant inhibited fibroblast [3H]thymidine incorporation. Examination of pre-S-phase events indicated stimulation of the immediate response gene, c-fos, and no effect on the G1/S cyclin, cyclin D1, suggesting that the surfactant block occurred elsewhere before S phase. The antioxidant N-acetyl-L-cysteine (NAC), like surfactant, inhibited [3H]thymidine incorporation. Furthermore, menadione, a generator of intracellular H2O2, stimulated fibroblast [3H]thymidine incorporation, and this was inhibited by surfactant. Interleukin-1 (IL-1)-stimulated secretion of the inflammatory mediators, IL-6 and prostaglandin E2, was also inhibited by surfactant. These data suggest that surfactant may modify lung fibroblast participation in ARDS sequelae by downregulating DNA synthesis and secondary inflammatory mediator production.

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