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The Journal of Gene Medicine Mar 2021Pulmonary fibrosis is characterized by progressive and irreversible scarring in the lungs with poor prognosis and treatment. It is caused by various factors, including... (Review)
Review
Pulmonary fibrosis is characterized by progressive and irreversible scarring in the lungs with poor prognosis and treatment. It is caused by various factors, including environmental and occupational exposures, and some rheumatic immune diseases. Even the rapid global spread of the COVID-19 pandemic can also cause pulmonary fibrosis with a high probability. Functions attributed to long non-coding RNAs (lncRNAs) make them highly attractive diagnostic and therapeutic targets in fibroproliferative diseases. Therefore, an understanding of the specific mechanisms by which lncRNAs regulate pulmonary fibrotic pathogenesis is urgently needed to identify new possibilities for therapy. In this review, we focus on the molecular mechanisms and implications of lncRNAs targeted protein-coding and non-coding genes during pulmonary fibrogenesis, and systematically analyze the communication of lncRNAs with various types of RNAs, including microRNA, circular RNA and mRNA. Finally, we propose the potential approach of lncRNA-based diagnosis and therapy for pulmonary fibrosis. We hope that understanding these interactions between protein-coding and non-coding genes will contribute to the development of lncRNA-based clinical applications for pulmonary fibrosis.
Topics: Gene Expression Regulation; Genetic Markers; Genetic Therapy; Humans; MicroRNAs; Proteins; Pulmonary Fibrosis; RNA, Circular; RNA, Long Noncoding
PubMed: 33533071
DOI: 10.1002/jgm.3318 -
Stem Cell Research & Therapy Nov 2020Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to...
BACKGROUND
Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis.
METHODS
We investigated the transplantation of MenSCs in a pulmonary fibrosis mouse model induced by BLM. Mouse was divided into three groups: control group, BLM group, MenSC group. Twenty-one days after MenSC transplantation, we examined collagen content, pathological, fibrosis area in the lung tissue, and the level of inflammatory factors of serum. RNA sequence was used to examine the differential expressed gene between three groups. Transwell coculture experiments were further used to examine the function of MenSCs to MLE-12 cells and mouse lung fibroblasts (MLFs) in vitro.
RESULTS
We observed that transplantation of MenSCs significantly improves pulmonary fibrosis mouse through evaluations of pathological lesions, collagen deposition, and inflammation. Transwell coculturing experiments showed that MenSCs suppress the proliferation and the differentiation of MLFs and inhibit the apoptosis of MLE-12 cells. Furthermore, antibody array results demonstrated that MenSCs inhibit the apoptosis of MLE-12 cells by suppressing the expression of inflammatory-related cytokines, including RANTES, Eotaxin, GM-CSF, MIP-1γ, MCP-5, CCL1, and GITR.
CONCLUSIONS
Collectively, our results suggested MenSCs have a great potential in the treatment of pulmonary fibrosis, and cytokines revealed in antibody array are expected to become the target of future therapy of MenSCs in clinical treatment of pulmonary fibrosis.
Topics: Animals; Anti-Inflammatory Agents; Bleomycin; Humans; Menstruation; Mice; Pulmonary Fibrosis; Stem Cells
PubMed: 33176882
DOI: 10.1186/s13287-020-01926-x -
Trends in Molecular Medicine Apr 2016Pulmonary fibrosis (PF) is a growing clinical problem which can result in breathlessness or respiratory failure and has an average life expectancy of 3 years from... (Review)
Review
Pulmonary fibrosis (PF) is a growing clinical problem which can result in breathlessness or respiratory failure and has an average life expectancy of 3 years from diagnosis. Therapeutic options for PF are limited and there is therefore a significant unmet clinical need. The recent resurgent interest in macrophage biology has led to a new understanding of lung macrophage origins, biology, and phenotypes. In this review we discuss fibrotic mechanisms and focus on the role of macrophages during fibrotic lung disease. Data from both human and murine studies are reviewed, highlighting novel macrophage-orientated biomarkers for disease diagnosis and potential targets for future anti-fibrotic therapies.
Topics: Animals; Biomarkers; Cell- and Tissue-Based Therapy; Cytokines; Humans; Immunotherapy; Inflammation Mediators; Macrophage Activation; Macrophages, Alveolar; Phenotype; Pulmonary Fibrosis; T-Lymphocyte Subsets
PubMed: 26979628
DOI: 10.1016/j.molmed.2016.02.004 -
The European Respiratory Journal May 2013Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal... (Review)
Review
Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal lung architecture and finally death. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the delineation of primary pathways has proven to be elusive. In this review susceptibility and injurious agents, such as viruses and gastro-oesophageal reflux, and their probable role in initiating disease will be discussed. Further topics that are elaborated are candidate ancillary pathways, including immune mechanisms, oxidative and endoplasmic reticulum stress, activation of the coagulation cascade and the potential role of stem cells. This review will try to provide the reader with an integrated view on the current knowledge and attempts to provide a road map for future research. It is important to explore robust models of overall pathogenesis, reconciling a large number of clinical and scientific observations. We believe that the integration of current data into a "big picture" overview of fibrogenesis is essential for the development of effective antifibrotic strategies. The latter will probably consist of a combination of agents targeting a number of key pathways.
Topics: Animals; Blood Coagulation; Disease Progression; Endoplasmic Reticulum Stress; Epithelial Cells; Gastroesophageal Reflux; Genetic Predisposition to Disease; Humans; Mice; Mutation; Oxidative Stress; Pulmonary Alveoli; Pulmonary Fibrosis; Stem Cells
PubMed: 23100500
DOI: 10.1183/09031936.00073012 -
Biochimica Et Biophysica Acta.... Sep 2017DNA methylation is a major epigenetic mechanism to regulate gene expression. Epigenetic regulation, including DNA methylation, histone modifications and RNA... (Review)
Review
DNA methylation is a major epigenetic mechanism to regulate gene expression. Epigenetic regulation, including DNA methylation, histone modifications and RNA interference, results in heritable changes in gene expression independent of alterations in DNA sequence. Epigenetic regulation often occurs in response to aging and environment stimuli, including exposures and diet. Studies have shown that DNA methylation is critical in the pathogenesis of fibrosis involving multiple organ systems, contributing to significant morbidity and mortality. Aberrant DNA methylation can silence or activate gene expression patterns that drive the fibrosis process. Fibrosis is a pathological wound healing process in response to chronic injury. It is characterized by excessive extracellular matrix production and accumulation, which eventually affects organ architecture and results in organ failure. Fibrosis can affect a wide range of organs, including the heart and lungs, and have limited therapeutic options. DNA methylation, like other epigenetic process, is reversible, therefore regarded as attractive therapeutic interventions. Although epigenetic mechanisms are highly interactive and often reinforcing, this review discusses DNA methylation-dependent mechanisms in the pathogenesis of organ fibrosis, with focus on cardiac and pulmonary fibrosis. We discuss specific pro- and anti-fibrotic genes and pathways regulated by DNA methylation in organ fibrosis; we further highlight the potential benefits and side-effects of epigenetic therapies in fibrotic disorders.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Extracellular Matrix; Heart Diseases; Humans; Pulmonary Fibrosis
PubMed: 28501566
DOI: 10.1016/j.bbadis.2017.05.010 -
Thorax Mar 1968Histological changes attributable to busulphan were found at necropsy in the lungs of six out of 14 cases of chronic granulocytic leukaemia. The alveoli contained...
Histological changes attributable to busulphan were found at necropsy in the lungs of six out of 14 cases of chronic granulocytic leukaemia. The alveoli contained persistent fibrinous oedema converting to fibrous tissue, and also atypical cells. Only one out of seven controls with leukaemia showed fibrinous oedema, and atypical cells were absent. In the lungs from rare cases of fatal pulmonary fibrosis due to busulphan, the histological changes were similar but more severe. It is concluded that busulphan commonly causes fibrinous oedema in chronic granulocytic leukaemia and on rare occasions it becomes severe or persistent enough to cause fatal fibrosis of the lungs. The name busulphan lung is suggested for any of these changes. The term `intra-alveolar fibrosis' should be used instead of `interstitial fibrosis', as it had been called by most previous authors. Despite these findings we consider that this valuable drug should be discontinued only in those very rare instances when intra-alveolar fibrosis shows signs of becoming disabling.
Topics: Humans; Leukemia, Myeloid; Lung; Male; Pulmonary Fibrosis
PubMed: 5240498
DOI: 10.1136/thx.23.2.187 -
The European Respiratory Journal Jan 2017
Topics: Humans; Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis
PubMed: 28100552
DOI: 10.1183/13993003.02202-2016 -
Scientific Reports Nov 2021Idiopathic pulmonary fibrosis is a lethal lung fibroproliferative disease with limited therapeutic options. Differential expression profiling of affected sites has been...
Idiopathic pulmonary fibrosis is a lethal lung fibroproliferative disease with limited therapeutic options. Differential expression profiling of affected sites has been instrumental for involved pathogenetic mechanisms dissection and therapeutic targets discovery. However, there have been limited efforts to comparatively analyse/mine the numerous related publicly available datasets, to fully exploit their potential on the validation/creation of novel research hypotheses. In this context and towards that goal, we present Fibromine, an integrated database and exploration environment comprising of consistently re-analysed, manually curated transcriptomic and proteomic pulmonary fibrosis datasets covering a wide range of experimental designs in both patients and animal models. Fibromine can be accessed via an R Shiny application ( http://www.fibromine.com/Fibromine ) which offers dynamic data exploration and real-time integration functionalities. Moreover, we introduce a novel benchmarking system based on transcriptomic datasets underlying characteristics, resulting to dataset accreditation aiming to aid the user on dataset selection. Cell specificity of gene expression can be visualised and/or explored in several scRNA-seq datasets, in an effort to link legacy data with this cutting-edge methodology and paving the way to their integration. Several use case examples are presented, that, importantly, can be reproduced on-the-fly by a non-specialist user, the primary target and potential user of this endeavour.
Topics: Animals; Databases, Factual; Humans; Mice; Pulmonary Fibrosis
PubMed: 34741074
DOI: 10.1038/s41598-021-01069-w -
Molecular Immunology Nov 2022Mesenchymal stem cells (MSCs) are promising remedies for various inflammatory disease including pulmonary fibrosis (PF). However, the properties of MSCs in PF...
Autophagy inhibition restores CD200 expression under IL-1β microenvironment in placental mesenchymal stem cells of fetal origin and improves its pulmonary fibrosis therapeutic potential.
BACKGROUND
Mesenchymal stem cells (MSCs) are promising remedies for various inflammatory disease including pulmonary fibrosis (PF). However, the properties of MSCs in PF pathological microenvironment remain unclear. In this study, the efficacy of autophagy in placental mesenchymal stem cells of fetal origin (fPMSCs) in either IL-1β treatment or BLM induced pulmonary fibrosis mice model was examined.
METHODS
The characteristic of fPMSCs was identified by morphological observation, flow cytometry and differentiation potential. In vitro experiments, fPMSCs were stimulated with IL-1β, to mimic inflammatory microenvironment of pulmonary fibrosis. The immunosuppressive properties and autophagic function in fPMSCs treated with IL-1β were evaluated by both macrophage cells THP-1 activation and the expression of CD200 situation, autophagy marker and MAPK signaling pathway. The in vivo anti-fibrotic activity of fPMSCs interfering autophagy was evaluated by using BLM induced pulmonary fibrosis mice model.
RESULTS
fPMSCs belonged to CD73CD90CD105/CD14 CD34CD45HLA-DR cells, and capable differentiation to adipogenic, osteogenic and chondrogenic cells. In addition, immunoinhibitory activity of fPMSCs for macrophage was restrained by IL-1β treatment in CD200 dependent manner. Suppression of autophagy by sh-Atg5 lentivirus increased the expression of CD200 and ratio of CD200 positive fPMSCs, and enhanced fPMSCs immunosuppression for THP-1 activation. Mechanistically, IL-1β induced autophagy regulated by p38 signaling cascade. In vivo, autophagy inhibition induced by Atg5 knockdown in fPMSCs resulted in strengthening antifibrotic effects on PF mice model.
CONCLUSIONS
Collectively, autophagy derived from inflammatory microenvironment hampered the immunoinhibitory properties of MSCs. Based on this, adjustment of autophagy may be a valid approach to facilitate their immunomodulatory and anti-fibrotic efficacy.
Topics: Animals; Autophagy; Female; Fetus; Mesenchymal Stem Cells; Mice; Placenta; Pregnancy; Pulmonary Fibrosis
PubMed: 36075140
DOI: 10.1016/j.molimm.2022.08.014 -
Respiration; International Review of... 2013Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal disease, with a highly variable course in individual patients. Episodes of rapid... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal disease, with a highly variable course in individual patients. Episodes of rapid deterioration are not uncommon, often following a period of stability. In cases of uncertain etiology, with typical clinical and high-resolution computed tomography (HRCT) features, the term 'acute exacerbation of IPF' (AE-IPF) has been coined to describe a combination of diffuse alveolar damage and preexisting usual interstitial pneumonia. In 2007, a consensus definition and diagnostic criteria were proposed. Although the presence of overt infection is currently an exclusion criterion, it appears likely that occult infection, reflux and thoracic surgical procedures are all trigger factors for AE-IPF. The development of new, usually bilateral infiltrates (ground-glass attenuation with variable admixed consolidation) is a defining HRCT feature. The outcome is poor with a short-term mortality in excess of 50% despite therapy. A number of pathophysiologic pathways are activated, with immunologic dysregulation, epithelial damage and circulating fibrocytes all believed to play a pathogenetic role. Acute exacerbations are less prevalent in other fibrotic lung diseases than in IPF and may have a better outcome, with the exception of acute exacerbations of rheumatoid lung. In AE-IPF, the exclusion of alternative causes of rapid deterioration, including heart failure and infection, is the main goal of investigation. Empirical high-dose corticosteroid steroid therapy is generally used in AE-IPF, without proven benefit.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Terminology as Topic; Tomography, X-Ray Computed
PubMed: 24157720
DOI: 10.1159/000355485