scholarly journals A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

2017 ◽  
Vol 26 (144) ◽  
pp. 160125 ◽  
Author(s):  
Gianluca Bagnato ◽  
William Neal Roberts ◽  
Jesse Roman ◽  
Sebastiano Gangemi
Keyword(s):  
Systematic Review ◽  
Systemic Sclerosis ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Therapeutic Potential ◽  
Messenger Rnas ◽  
Rna Sequences ◽  
Non Coding Rna ◽  
Evolutionarily Conserved

Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20–23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential.

scholarly journals PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea Doni ◽  
Alberto Mantovani ◽  
Barbara Bottazzi ◽  
Remo Castro Russo
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Life Quality ◽  
Unknown Origin ◽  
Protective Role

PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient’s life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.

scholarly journals Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis

Thorax ◽  
2013 ◽  
Vol 68 (5) ◽  
pp. 436-441 ◽  
Author(s):  
Carmel J Stock ◽  
Hiroe Sato ◽  
Carmen Fonseca ◽  
Winston A S Banya ◽  
Philip L Molyneaux ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Promoter Polymorphism

Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elena Aloisio ◽  
Federica Braga ◽  
Chiara Puricelli ◽  
Mauro Panteghini
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Binary Data ◽  
Meta Analysis ◽  
Mortality Prediction ◽  
Asian Populations ◽  
Increased Risk ◽  
Using Data ◽  
Patient Prognosis

Abstract Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear. Methods We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI). Results Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22–6.06; p=0.015). However, a high degree of heterogeneity (I2=85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60–82%) and a specificity of 60% (CI 52–68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983–1.036; p=0.505). Conclusions Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations.

scholarly journals Breath Biomarkers in Idiopathic Pulmonary Fibrosis: A Systematic Review

2018 ◽  
Author(s):  
Conal Hayton ◽  
Dayle Terrington ◽  
Andrew M. Wilson ◽  
Nazia Chaudhuri ◽  
Colm Leonard ◽  
...  
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis

scholarly journals Efficacy and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis patients: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e050004
Author(s):  
Wenjuan Wu ◽  
Lingxiao Qiu ◽  
Jizhen Wu ◽  
Xueya Liu ◽  
Guojun Zhang
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Acute Exacerbation ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomised Controlled

ObjectivesIdiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a common histological pattern of interstitial pneumonia. To analyse the efficacy and safety of pirfenidone in the treatment of IPF, a systematic review and meta-analysis was performed.DesignThis is a meta-analysis study.ParticipantsPatients were diagnosed as IPF.InterventionsUse of pirfenidone.Primary and secondary outcomeProgression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.MeasuresThe inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.ResultsA total of 9 randomised controlled trials with 1011 participants receiving pirfenidone and 912 controls receiving placebo were summarised. The pooled result suggested a statistically significant difference inall-cause mortality after pirfenidone use, with a summarised relative ratio of 0.51 (p<0.01). Longer PFS was observed in patients receiving pirfenidone compared with those who were given placebo (p<0.01). The IPF groups presented a high incidence of adverse events with a pooled relative ratio of 3.89 (p<0.01).ConclusionsPirfenidone can provide survival benefit for patients with IPF. Pirfenidone treatment was also associated with a longer PFS, a lower incidence of acute exacerbation and worsening of IPF.

scholarly journals Effects of Nintedanib on Quantitative Lung Fibrosis Score in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 14 (1) ◽  
pp. 22-31
Author(s):  
Lisa Lancaster ◽  
Jonathan Goldin ◽  
Matthias Trampisch ◽  
Grace Hyun Kim ◽  
Jonathan Ilowite ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Lung Fibrosis ◽  
Open Label ◽  
High Resolution Computed Tomography ◽  
Double Blind ◽  
Phase Iiib ◽  
Exploratory Data ◽  
Relative Change

Background: Nintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied. Objective: We conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF. Methods: 113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory. Results: Adjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: −9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: −1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were −14.2 mL and −83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: −8.7, 146.8]). Conclusion: Exploratory data suggest that in patients with IPF, 6 months’ treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.

scholarly journals Targeting the DNM3OS / miR-199a~214 cluster for the treatment of fibroproliferative diseases

2018 ◽  
Author(s):  
G. Savary ◽  
M. Buscot ◽  
E. Dewaeles ◽  
S. Diazzi ◽  
N. Nottet ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mature Mirnas ◽  
Kidney Fibrosis ◽  
Downstream Effector ◽  
Non Coding Rna ◽  
Fibrotic Diseases ◽  
Fibrotic Disorders ◽  
Long Non Coding Rna ◽  
Lung And Kidney

AbstractGiven the paucity of effective treatments for fibrotic disorders, new insights into the deleterious mechanisms controlling fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. Here, we identified the long non-coding RNA DNM3OS as a critical downstream effector of TGF-β-induced myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to 3 distinct profibrotic mature miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which influence both SMAD and non-SMAD components of TGF-β signaling in a multifaceted way, through two modes of action consisting of either signal amplification or mediation. Finally, we provide preclinical evidence that interfering with DNM3OS function using distinct strategies not only prevents lung and kidney fibrosis but also improves established lung fibrosis, providing thus a novel paradigm for the treatment of refractory fibrotic diseases such as idiopathic pulmonary fibrosis.One Sentence SummaryThe DNM3OS lncRNA is a reservoir of fibromiRs with major functions in fibroblast response to TGF-β and represents a valuable therapeutic target for refractory fibrotic diseases such as idiopathic pulmonary fibrosis (IPF).

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