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Pulmonary fibrosis AND MicroRNA

Mariola Kurowska-Stolarska, Manhl K Hasoo, David J Welsh, Lynn Stewart, Donna McIntyre, Brian E Morton, Steven Johnstone, Ashley M Miller, Darren L Asquith, Neal L Millar, Ann B Millar, Carol A Feghali-Bostwick, Nikhil Hirani, Peter J Crick, Yuqin Wang, William J Griffiths, Iain B McInnes, Charles McSharry
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways. OBJECTIVES: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis...
October 13, 2016: Journal of Allergy and Clinical Immunology
Dhamotharan Pattarayan, Rajesh K Thimmulappa, Vilwanathan Ravikumar, Subbiah Rajasekaran
Lack of markers of subclinical disease state and clinical phenotype other than pulmonary function test has made the diagnosis and interventions of environmental respiratory diseases a major challenge. MicroRNAs (miRNAs), small non-coding single stranded RNAs, have emerged as potential disease-modifier in various environmental respiratory diseases. They can also be found in various body fluids and are remarkably stable. Because of their high stability, disease-specific expression, and the ease to detect and quantify them have raised the potential of miRNAs in body fluids to be useful clinical diagnostic biomarkers for lung disease phenotyping...
September 27, 2016: Clinical Reviews in Allergy & Immunology
Tomonori Makiguchi, Mitsuhiro Yamada, Yusuke Yoshioka, Hisatoshi Sugiura, Akira Koarai, Shigeki Chiba, Naoya Fujino, Yutaka Tojo, Chiharu Ota, Hiroshi Kubo, Seiichi Kobayashi, Masaru Yanai, Sanae Shimura, Takahiro Ochiya, Masakazu Ichinose
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis. Although the median survival is 3 years, the clinical course varies to a large extent among IPF patients. To date, there has been no definitive prognostic marker. Extracellular vesicles (EVs) are known to hold nucleic acid, including microRNAs, and to regulate gene expression in the recipient cells. Moreover, EVs have been shown to express distinct surface proteins or enveloped microRNAs depending on the parent cell or pathological condition...
2016: Respiratory Research
Klara Piletič, Tanja Kunej
MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene...
October 2016: Archives of Toxicology
Yi-Chun Wang, Jing-Shi Liu, Hao-Ke Tang, Jing Nie, Ji-Xian Zhu, Ling-Ling Wen, Qu-Lian Guo
MicroRNA (miR)-221 plays an essential role in the epithelial-mesenchymal transition (EMT). High mobility group AT-hook 2 (HMGA2), is a key regulator of EMT. However, the role of miR‑221 in pulmonary fibrosis, and the association between miR‑221 and HMGA2 remain largely unknown. For this purpose, we examined the expression of miR‑221 and HMGA2 in human idiopathic pulmonary fibrosis (IPF) tissues and pulmonary cells, namely the adenocarcinoma A549 and human bronchial epithelium (HBE) cell lines, and found that the expression of miR‑221 was inhibited in both tissues and cells whereas high mRNA and protein expression of HMGA2 was observed...
October 2016: International Journal of Molecular Medicine
Yi Zhuang, Jinghong Dai, Yongsheng Wang, Huan Zhang, Xinxiu Li, Chunli Wang, Mengshu Cao, Yin Liu, Jingjing Ding, Hourong Cai, Deping Zhang, Yaping Wang
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease involving pulmonary injury associated with tissue repair, dysfunction and fibrosis. Recent studies indicate that some microRNAs (miRNAs) may play critical roles in the pathogenesis of pulmonary fibrosis. In this study, we aim to investigate whether miR-338* (miR-338-5p), which has been found to be associated with tumor progression, is associated with pathological process of pulmonary fibrosis. Balb/c mice were treated with bleomycin (BLM) to establish IPF models...
2016: American Journal of Translational Research
Yi Zhuang, Jinghong Dai, Yongsheng Wang, Huan Zhang, Xinxiu Li, Chunli Wang, Mengshu Cao, Yin Liu, Hourong Cai, Deping Zhang, Yaping Wang
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease involving pulmonary injury associated with tissue repair, dysfunction and fibrosis. MicroRNAs (miRNAs), as gene regulators, are assumed to regulate about one third of genes and thus play important roles in cellular functions including proliferation, growth, differentiation and apoptosis. Recent studies have indicated that some miRNAs may play critical roles in the pathogenesis of pulmonary fibrosis. In this study, we found that miR-338*(miR-338-5p), which has been found to be associated with tumor progression, was down-regulated in fibroblasts and TGF-β-induced lung fibrotic tissues...
2016: American Journal of Translational Research
Qiuyun Wu, Lei Han, Weiwen Yan, Xiaoming Ji, Ruhui Han, Jingjin Yang, Jiali Yuan, Chunhui Ni
Silicosis is an incurable occupational disease associated with inflammation, fibroblast proliferation and the accumulation of extracellular matrix in lung tissues. The dysregulation of lncRNAs and miRNAs has been implicated in many complex diseases; however, the current understanding of their roles in fibrotic lung diseases, especially silicosis, remains limited. Our previous microRNA (miRNA, miR) microarray data have indicated decreased expression levels of miR-489 in lung tissues of silica-induced pulmonary fibrosis...
2016: Scientific Reports
Keiko Mizuno, Hiroko Mataki, Naohiko Seki, Tomohiro Kumamoto, Kazuto Kamikawaji, Hiromasa Inoue
In spite of advances in the diagnosis and current molecular target therapies of lung cancer, this disease remains the most common cause of cancer-related death worldwide. Approximately 80% of lung cancers is non-small cell lung cancer (NSCLC), and 5-year survival rate of the disease is ~20%. On the other hand, idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology. IPF is refractory to treatment and has a very low survival rate. Moreover, IPF is frequently associated with lung cancer...
August 4, 2016: Journal of Human Genetics
Kazuto Kamikawaji, Naohiko Seki, Masaki Watanabe, Hiroko Mataki, Tomohiro Kumamoto, Koichiro Takagi, Keiko Mizuno, Hiromasa Inoue
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that is refractory to treatment and carries a high mortality rate. IPF is frequently associated with lung cancer. Identification of molecular targets involved in both diseases may elucidate novel molecular mechanisms contributing to their pathology. Recent studies of microRNA (miRNA) expression signatures showed that microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this study was to investigate the functional significance of miR-29a in lung cancer cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular targets modulated by miR-29a in these cells...
August 4, 2016: Journal of Human Genetics
Moisés Selman, Carlos López-Otín, Annie Pardo
Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal disease of unknown aetiology. A growing body of evidence supports that IPF represents an epithelial-driven process characterised by aberrant epithelial cell behaviour, fibroblast/myofibroblast activation and excessive accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The mechanisms involved in the abnormal hyper-activation of the epithelium are unclear, but we propose that recapitulation of pathways and processes critical to embryological development associated with a tissue specific age-related stochastic epigenetic drift may be implicated...
August 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Supparerk Disayabutr, Eun Kyung Kim, Seung-Ick Cha, Gary Green, Ram P Naikawadi, Kirk D Jones, Jeffrey A Golden, Aaron Schroeder, Michael A Matthay, Jasleen Kukreja, David J Erle, Harold R Collard, Paul J Wolters
Pathologic features of idiopathic pulmonary fibrosis (IPF) include genetic predisposition, activation of the unfolded protein response, telomere attrition, and cellular senescence. The mechanisms leading to alveolar epithelial cell (AEC) senescence are poorly understood. MicroRNAs (miRNAs) have been reported as regulators of cellular senescence. Senescence markers including p16, p21, p53, and senescence-associated β-galactosidase (SA-βgal) activity were measured in type II AECs from IPF lungs and unused donor lungs...
2016: PloS One
Ning-Yuan Chen, Scott D Collum, Fayong Luo, Tingting Weng, Thuy-Trahn Le, Adriana M Hernandez, Kemly Philip, Jose G Molina, Luis J Garcia-Morales, Yanna Cao, Tien C Ko, Javier Amione-Guerra, Odeaa Al-Jabbari, Raquel R Bunge, Keith Youker, Brian A Bruckner, Rizwan Hamid, Jonathan Davies, Neeraj Sinha, Harry Karmouty-Quintana
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. The development of pulmonary hypertension (PH) is considered the single most significant predictor of mortality in patients with chronic lung diseases. The processes that govern the progression and development of fibroproliferative and vascular lesions in IPF are not fully understood. Using human lung explant samples from patients with IPF with or without a diagnosis of PH as well as normal control tissue, we report reduced BMPR2 expression in patients with IPF or IPF+PH...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Zhen Yang, Qian Li, Sanqiao Yao, Ge Zhang, Rong Xue, Guoliang Li, Yizheng Wang, Shixin Wang, Ruichang Wu, Hongsheng Gao
The accumulated data indicate that there is significant genetic heterogeneity underlying the etiology of silicosis. Recent reports have revealed that microRNAs (miRNAs) play an important role in regulating pulmonary fibrosis. This study, therefore, aimed to identify some miRNAs as biomarkers for silicosis, and to explore the early diagnostic value of biomarkers for silicosis. Total RNAs were collected from the peripheral blood leukocytes of 23 silicosis patients and 23 healthy controls, the different miRNAs were screened using microarrays...
September 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Ok-Seon Kwon, Keun-Tae Kim, Eunioo Lee, Myoungjae Kim, Seo-Hyun Choi, Henghong Li, Albert J Fornace, Jae-Ho Cho, Yun-Sil Lee, Ji-Seon Lee, Yoon-Jin Lee, Hyuk-Jin Cha
Radiation-induced lung fibrosis, the most serious effect of lung cancer radiotherapy on normal tissue, remains a major technical obstacle to the broader application of radiotherapy to patients with lung cancer. This study describes the use of an image-guided irradiation system in mice mimicking stereotactic body radiotherapy (SBRT) to examine the molecular features of chronic fibrotic response after radiation injury. MicroRNA (miR) array analysis of injured pulmonary tissue identified a set of miRs whose expression was significantly increased in damaged lung tissue...
2016: PloS One
Udit Agarwal, Amanda W Smith, Kristin M French, Archana V Boopathy, Alex George, David Trac, Milton E Brown, Ming Shen, Rong Jiang, Janet D Fernandez, Brian E Kogon, Kirk R Kanter, Baahaldin Alsoufi, Mary B Wagner, Manu O Platt, Michael E Davis
UNLABELLED: Children with congenital heart diseases have increased morbidity and mortality, despite various surgical treatments, therefore warranting better treatment strategies. Here we investigate the role of age of human pediatric cardiac progenitor cells (hCPCs) on ventricular remodeling in a model of juvenile heart failure. hCPCs isolated from children undergoing reconstructive surgeries were divided into 3 groups based on age: neonate (1 day to 1 month), infant (1 month to 1 year), and child (1 to 5 years)...
July 2016: Stem Cells Translational Medicine
Rebecca L Kusko, John F Brothers Ii, John Tedrow, Kusum Pandit, Luai Huleihel, Catalina Perdomo, Gang Liu, Brenda Juan-Guardela, Daniel Kass, Sherry Zhang, Marc Lenburg, Fernando Martinez, John Quackenbush, Frank Sciurba, Andrew Limper, Mark Geraci, Ivana Yang, David A Schwartz, Jennifer Beane, Avrum Spira, Naftali Kaminski
RATIONALE: Despite shared environmental exposures, IPF and COPD are usually studied in isolation and the presence of shared molecular mechanisms is unknown. OBJECTIVES: We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and idiopathic pulmonary fibrosis (IPF). METHODS: We defined the transcriptional repertoire of COPD, IPF or normal histology lungs using RNA-seq (n=87). MEASUREMENTS AND MAIN RESULTS: Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n=193)...
April 22, 2016: American Journal of Respiratory and Critical Care Medicine
Shuhong Li, Jing Geng, Xuefeng Xu, Xiaoxi Huang, Dong Leng, Dingyuan Jiang, Jiurong Liang, Chen Wang, Dianhua Jiang, Huaping Dai
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal fibrotic lung disease with largely unknown etiology and pathogenesis. Evidence suggests microRNAs (miRNA) contribute to pathogenesis of IPF. In this study, we sought to identify miRNA expression signatures and determine the role of miR-130b-3p in lung fibrosis. The miRNA expression profile of the lungs from patients with IPF and normal donors was determined by Affymetrix microarray, and transcriptome with Affymetrix array. The functions and signal pathways as well as miRNA-mRNA networks were established by bioinformatics analysis...
2016: PloS One
Yen-Chou Chen, Bing-Chang Chen, Chung-Chi Yu, Shin-Hua Lin, Chien-Huang Lin
Although microRNA (miRNA) dysregulation with intracellular signaling cascade disruption has been demonstrated in the pathophysiology of pulmonary fibrosis, the relationship between miRNAs and intracellular signaling cascades in pulmonary fibrosis remains unclear. Using the human embryonic lung fibroblast cell line WI-38, we observed endothelin-1 (ET-1)- and thrombin-induced expression of the differentiation markers α-smooth muscle actin (α-SMA) and vimentin along with increased connective tissue growth factor (CTGF) protein expression...
October 2016: Journal of Cellular Physiology
Steven Maltby, Maximilian Plank, Hock L Tay, Adam Collison, Paul S Foster
MicroRNAs (miRNAs) are small non-coding RNA molecules that modulate expression of the majority of genes by inhibiting protein translation. Growing literature has identified functional roles for miRNAs across a broad range of biological processes. As such, miRNAs are recognized as potential disease biomarkers and novel targets for therapies. While several miRNA-targeted therapies are currently in clinical trials (e.g., for the treatment of hepatitis C virus infection and cancer), no therapies have targeted miRNAs in respiratory diseases in the clinic...
2016: Frontiers in Physiology
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