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Pulmonary fibrosis AND MicroRNA

Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
S N Sunilgowda, Devipriya Nagarajan, Devipriya Nagarajan
Radiotherapy is the most widely used treatment method for average and advanced lung cancer patients. Moreover, the clinical toxicities caused by radiotherapy are categorized into acute radiation pneumonitis and late pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is a complex physiological process involves many signaling molecules and proteins like adaptor proteins, and transcriptional factors. It was identified as a significant mechanism for fibrosis, wound healing and also cancer. A variety of biomarkers have appeared in radiation-induced lung EMT, some of which are acquired (N-cadherin, vimentin and fibronectin, etc...
February 6, 2018: Current Drug Targets
Eleni Chouri, Nila H Servaas, Cornelis P J Bekker, Alsya J Affandi, Marta Cossu, Maarten R Hillen, Chiara Angiolilli, Jorre S Mertens, Lucas L van den Hoogen, Sandra Silva-Cardoso, Maarten van der Kroef, Nadia Vazirpanah, Catharina G K Wichers, Tiago Carvalheiro, Sofie L M Blokland, Barbara Giovannone, Laura Porretti, Wioleta Marut, Barbara Vigone, Joel A G van Roon, Lorenzo Beretta, Marzia Rossato, Timothy R D J Radstake
OBJECTIVE: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. METHODS: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR...
January 19, 2018: Journal of Autoimmunity
Jongmin Kim
The endothelial to mesenchymal transition (EndMT) is a newly recognized, fundamental biological process involved in development and tissue regeneration, as well as pathological processes such as the complications of diabetes, fibrosis and pulmonary arterial hypertension. The EndMT process is tightly controlled by diverse signaling networks, similar to the epithelial to mesenchymal transition. Accumulating evidence suggests that microRNAs (miRNAs) are key regulators of this network, with the capacity to target multiple messenger RNAs involved in the EndMT process as well as in the regulation of disease progression...
January 22, 2018: BMB Reports
Da Young Shin, Mi Ho Jeong, In Jae Bang, Ha Ryong Kim, Kyu Hyuck Chung
Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted...
January 11, 2018: Toxicology Letters
Tzu-Pin Shentu, Tse-Shun Huang, Mateja Cernelc-Kohan, Joy Chan, Simon S Wong, Celia R Espinoza, Chunting Tan, Irene Gramaglia, Henri van der Heyde, Shu Chien, James S Hagood
Bone marrow-derived mesenchymal stem cells (MSC) have been promoted for multiple therapeutic applications. Many beneficial effects of MSCs are paracrine, dependent on extracellular vesicles (EVs). Although MSC-derived EVs (mEVs) are beneficial for acute lung injury and pulmonary fibrosis, mechanisms of mEV uptake by lung fibroblasts and their effects on myofibroblastic differentiation have not been established. We demonstrate that mEVs, but not fibroblast EVs (fEVs), suppress TGFβ1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts...
December 22, 2017: Scientific Reports
Kathrin Krause, Benjamin T Kopp, Mia F Tazi, Kyle Caution, Kaitlin Hamilton, Asmaa Badr, Chandra Shrestha, Dmitry Tumin, Don Hayes, Frank Robledo, Luanne Hall-Stoodley, Brett G Klamer, Xiaoli Zhang, Santiago Partida-Sanchez, Narasimham L Parinandi, Stephen E Kirkby, Duaa Dakhlallah, Karen S McCoy, Estelle Cormet-Boyaka, Amal O Amer
INTRODUCTION: Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17-92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function...
December 11, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Yongmei Cao, Yujing Liu, Feng Ping, Lyu Yi, Zhen Zeng, Yingchuan Li
Pulmonary fibrosis triggered during the early stage of acute respiratory distress syndrome (ARDS) contributes to poor prognosis in patients. However, whether microRNAs (miRNAs) can serve as therapeutic targets for early pulmonary fibrosis during ARDS is still largely unknown. In this study, we evaluated the effects and mechanisms of miR-200s and its targets ZEB1/2 in lung tissue. An early pulmonary fibrosis mouse model caused by ARDS was established via a lipopolysaccharide (LPS) three-hit regimen. Lentiviral packaged miR-200b/c cDNA or ZEB1/2 shRNA was intratracheally administered into the lungs of C57BL/6 mice 1 day before an LPS injection was administered...
March 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Hara Kang
Pulmonary fibrosis is the most common form of interstitial lung disease. The transforming growth factor-β (TGF-β) signaling pathway is extensively involved in the development of pulmonary fibrosis by inducing cell differentiation, migration, invasion, or hyperplastic changes. Accumulating evidence indicates that microRNAs (miRNAs) are dysregulated during the initiation of pulmonary fibrosis. miRNAs are small noncoding RNAs functioning as negative regulators of gene expression at the post-transcriptional level...
November 25, 2017: International Journal of Molecular Sciences
Lindsay R Stolzenburg, Ann Harris
Chronic respiratory diseases encompass a group of diverse conditions affecting the airways, which all impair lung function over time. They include cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma, which together affect hundreds of millions of people worldwide. MicroRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional gene repression, are now recognized as major regulators in the development and progression of chronic lung disease. Alterations in miRNA abundance occur in lung tissue, inflammatory cells, and freely circulating in blood and are thought to function both as drivers and modifiers of disease...
November 27, 2017: Biological Chemistry
Tsukasa Kadota, Yu Fujita, Yusuke Yoshioka, Jun Araya, Kazuyoshi Kuwano, Takahiro Ochiya
Aging is a major risk factor for the development of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. A main aspect of aging is the impaired function of maintaining homeostasis in the organs and body, which is associated with cellular senescence. Cellular senescence is recognized as the state of irreversible cell cycle arrest in response to a variety of cellular stresses. Senescent cells are not simply cell cycle-arrested cells; they also affect bystander cells through the secretion of bioactive molecules, termed the senescence-associated secretory phenotype (SASP)...
November 17, 2017: Molecular Aspects of Medicine
Huizhu Liu, Bingsi Wang, Jinjin Zhang, Songzi Zhang, Youlei Wang, Jie Zhang, Changjun Lv, Xiaodong Song
Emerging evidence suggests that microRNA (miRNA) and long noncoding RNA (lncRNA) play important roles in disease development. However, the mechanism underlying mRNA interaction with miRNA and lncRNA in idiopathic pulmonary fibrosis (IPF) remains unknown. This study presents a novel lnc-PCF that promotes the proliferation of TGF-β1-activated epithelial cells through the regulation of map3k11 by directly targeting miR-344a-5p during pulmonary fibrogenesis. Bioinformatics and in vitro translation assay were performed to confirm whether or not lnc-PCF is an actual lncRNA...
October 26, 2017: Cell Death & Disease
Huizhu Liu, Xueying Zhao, Jing Xiang, Jie Zhang, Chao Meng, Jinjin Zhang, Minge Li, Xiaodong Song, Changjun Lv
Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play increasingly important roles in pathological processes involved in disease development. However, whether mRNAs interact with miRNAs and lncRNAs to form an interacting regulatory network in diseases remains unknown. In this study, the interaction of coexpressed mRNAs, miRNAs and lncRNAs during tumor growth factor‑β1‑activated (TGF‑β1) epithelial‑mesenchymal transition (EMT) was systematically analyzed in human alveolar epithelial cells...
December 2017: Molecular Medicine Reports
E Karatzas, M M Bourdakou, G Kolios, G M Spyrou
Idiopathic Pulmonary Fibrosis (IPF) is a rare disease of the respiratory system in which the lungs stiffen and get scarred, resulting in breathing weakness and eventually leading to death. Drug repurposing is a process that provides evidence for existing drugs that may also be effective in different diseases. In this study, we present a computational pipeline having as input a number of gene expression datasets from early and advanced stages of IPF and as output lists of repurposed drugs ranked with a novel composite score...
October 3, 2017: Scientific Reports
Weiwen Yan, Qiuyun Wu, Wenxi Yao, Yan Li, Yi Liu, Jiali Yuan, Ruhui Han, Jingjin Yang, Xiaoming Ji, Chunhui Ni
Silicosis is a kind of chronic, progressive and incurable lung fibrotic diseases with largely unknown and complex pathogenesis and molecular mechanisms. Mounting evidence suggests that microRNAs (miRNAs, miRs) are involved in the pathogenesis of silicosis. Our previous study based on miRNA microarray had shown that the expression levels of miR-503 were down-regulated in mouse lung tissues of silica-induced pulmonary fibrosis. Here, we validated the decreased expression of miR-503 in the fibrotic mouse lung tissues, human bronchial epithelial cells (HBE) and human lung adenocarcinoma A549 cells which were exposed to silica...
September 12, 2017: Scientific Reports
Liqin Ren, Chunyan Yang, Yongfeng Dou, Renhui Zhan, Yi Sun, Yan Yu
AIM OF THE STUDY: Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung. MATERIALS AND METHODS: To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation...
August 17, 2017: Experimental Lung Research
Ting Xie, Jiurong Liang, Yan Geng, Ningshan Liu, Adrianne Kurkciyan, Vrishika Kulur, Dong Leng, Nan Deng, Zhenqiu Liu, Jianbo Song, Peter Chen, Paul W Noble, Dianhua Jiang
Successful repair and renewal of alveolar epithelial cells (AECs) are critical in prohibiting the accumulation of myofibroblasts in pulmonary fibrogenesis. MicroRNAs (miRNAs) are multifocal regulators involved in lung injury and repair. However, the contribution of miRNAs to AEC2 renewal and apoptosis is incompletely understood. We report that miRNA-29c (miR-29c) expression is lower in AEC2s of individuals with idiopathic pulmonary fibrosis than in healthy lungs. Epithelial cells overexpressing miR-29c show higher proliferative rates and viability...
December 2017: American Journal of Respiratory Cell and Molecular Biology
Chaoqun Huang, Xiao Xiao, Ye Yang, Amorite Mishra, Yurong Liang, Xiangming Zeng, Xiaoyun Yang, Dao Xu, Michael R Blackburn, Craig A Henke, Lin Liu
Aberrant proliferation and activation of lung fibroblasts contribute to the initiation and progression of idiopathic pulmonary fibrosis (IPF). However, the mechanisms responsible for the proliferation and activation of fibroblasts are not fully understood. The objective of this study was to investigate the role of miR-101 in the proliferation and activation of lung fibroblasts. miR-101 expression was determined in lung tissues from patients with IPF and mice with bleomycin-induced pulmonary fibrosis. The regulation of miR-101 and cellular signaling was investigated in pulmonary fibroblasts in vitro The role of miR-101 in pulmonary fibrosis in vivo was studied using adenovirus-mediated gene transfer in mice...
October 6, 2017: Journal of Biological Chemistry
F Guo, S C Lin, M S Zhao, B Yu, X Y Li, Q Gao, D J Lin
microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses...
July 3, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Carol M Artlett, Sihem Sassi-Gaha, Jennifer L Hope, Carol A Feghali-Bostwick, Peter D Katsikis
BACKGROUND: Despite the important role that microRNAs (miRNAs) play in immunity and inflammation, their involvement in systemic sclerosis (SSc) remains poorly characterized. miRNA-155 (miR-155) plays a role in pulmonary fibrosis and its expression can be induced with interleukin (IL)-1β. SSc fibroblasts have activated inflammasomes that are integrally involved in mediating the myofibroblast phenotype. In light of this, we investigated whether miR-155 played a role in SSc and if its expression was dependent on inflammasome activation...
June 17, 2017: Arthritis Research & Therapy
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