Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study

Duckworth, Anna; Gibbons, Michael; Allen, Richard J.; Almond, Howard; Beaumont, Robin N; Wood, Andrew R.; Lunnon, Katie; Lindsay, Mark A.; Wain, Louise V.; Tyrrell, Jess; Scotton, Chris J.

doi:10.1016/s2213-2600(20)30364-7

Cited by 133 publications

(89 citation statements)

References 51 publications

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“…PF is characterized by alveolar epithelial cell injury, remodeling of lung architecture, abnormal accumulation of extracellular matrix, and fibroblasts in parenchymal tissue [ 3 , 4 ], which ultimately results in respiratory failure and death [ 5 ]. The prognosis of IPF is poor, with a mortality rate comparable to advanced tumors [ 6 ]. In recent years, the treatments of medicine such as pirfenidone and nintedanib have improved lung function for patients with IPF [ 7 ], but neither one has a certain advantage on mortality outcomes, often necessitating lung transplantation [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies

Sun

et al. 2021

Stem Cell Res Ther

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Background Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF. Methods We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software. Results A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI −2.58 to −1.51, P < 0.001, I2 = 90%). Conclusions MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies

Sun

et al. 2021

Stem Cell Res Ther

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“…These findings point to a potential role for replicative senescence in IPF pathology. [17, 18, 19, 20, 21, 22, 23, 24, 25]. Furthermore, the elimination of senescent cells in a number of age-related diseases, such as cardiac fibrosis, pulmonary fibrosis, neurodegenerative diseases, osteoporosis, and metabolic disorders have been argued to alleviate the disease state [26].…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Hayflick Limit: Insights from an Integrated Analysis of Changing Transcripts, Proteins, Metabolites and Chromatin

Chan

Yuan

Soifer

et al. 2021

Preprint

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Replicative senescence (RS) as a model has become the central focus of research into cellular aging in vitro. Despite decades of study, this process through which cells cease dividing is not fully understood in culture, and even much less so in vivo during development and with aging. Here, we revisit Hayflicks original observation of RS in WI-38 human fetal lung fibroblasts equipped with a battery of high dimensional modern techniques and analytical methods to deeply profile the process of RS across each aspect of the central dogma and beyond. We applied and integrated RNA-seq, proteomics, metabolomics, and ATAC-seq to a high resolution RS time course. We found that the transcriptional changes that underlie RS manifest early, gradually increase, and correspond to a concomitant global increase in accessibility in nucleolar and lamin associated domains. During RS WI-38 fibroblast gene expression patterns acquire a striking resemblance to those of myofibroblasts in a process similar to the epithelial to mesenchymal transition (EMT). This observation is supported at the transcriptional, proteomic, and metabolomic levels of cellular biology. In addition, we provide evidence suggesting that this conversion is regulated by the transcription factors YAP1/TEAD1 and the signaling molecule TGFB-2.

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“…In recent years, the relationship between telomere length, DM and IPF has attracted attention. Elevated glucose and increased oxidative stress might interfere with telomerase function, thereby leading to shortened telomere length [ 58 ] and a mendelian randomisation study [ 59 ] inferred a causal link between shorter telomere length and higher risk of IPF.…”

Section: Discussionmentioning

confidence: 99%

Idiopathic pulmonary fibrosis and diabetes mellitus: a meta-analysis and systematic review

et al. 2021

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Background Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse interstitial lung disease, of which the etiology has been poorly understood. Several studies have focused on the relationship between IPF and diabetes mellitus (DM) in the past years but have failed to reach a consensus. This meta-analysis aimed to examine the association between diabetes to IPF. Methods We accumulated studies investigating the association between DM and IPF from databases including Medline, Cochrane Library, Embase, Web of Science, and China National Knowledge Infrastructure. RevMan 5.3 and the Newcastle–Ottawa Scale (NOS) were utilized to analyze the data and assess the quality of the included studies. The value of odds ratio (OR) with 95% confidence interval (CI) was used as the measure to estimate the risk of DM in IPF. Heterogeneity was assessed by I2 statistics. We also performed subgroup analysis, meta-regression, and Egger’s test for bias analysis. Results Nine case–control studies with 5096 IPF patients and 19,095 control subjects were included in the present meta-analysis, which indicated a positive correlation between DM and IPF (OR 1.65, 95% CI 1.30–2.10; P < 0.0001). Meta-regression and subgroup analysis negated the influence of covariates like cigarette smoking, age and gender, but the heterogeneity existed and could not be fully explained. Conclusion IPF and DM may be associated, but the causal relationship remains indeterminate till now. Further rigorously designed studies are required to confirm the present findings and investigate the possible mechanisms behind the effect of DM on IPF.

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Telomere length and risk of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease: a mendelian randomisation study

Cited by 133 publications

References 51 publications

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies

Revisiting the Hayflick Limit: Insights from an Integrated Analysis of Changing Transcripts, Proteins, Metabolites and Chromatin

Idiopathic pulmonary fibrosis and diabetes mellitus: a meta-analysis and systematic review

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