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https://www.readbyqxmd.com/read/27912147/inhibition-of-endocan-attenuates-monocrotaline-induced-connective-tissue-disease-related-pulmonary-arterial-hypertension
#1
Haiyan Zhao, Yunxin Xue, Yun Guo, Yue Sun, Dongmei Liu, Xiaofei Wang
Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#2
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27911098/siga-deficiency-in-individual-small-airways-is-associated-with-persistent-inflammation-and-remodeling
#3
Vasiliy V Polosukhin, Bradley W Richmond, Rui-Hong Du, Justin M Cates, Pingsheng Wu, Hui Nian, Pierre P Massion, Lorraine B Ware, Jae Woo Lee, Alexey V Kononov, William E Lawson, Timothy S Blackwell
RATIONALE: Maintenance of a surface immune barrier is important for homeostasis in organs with mucosal surfaces that interface with the external environment; however, the role of the mucosal immune system in chronic lung diseases is incompletely understood. OBJECTIVES: We examined the relationship between secretory immunoglobulin A (SIgA) on the mucosal surface of small airways and parameters of inflammation and airway wall remodeling in chronic obstructive pulmonary disease (COPD)...
December 2, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#4
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27905542/defining-an-olfactory-receptor-function-in-airway-smooth-muscle-cells
#5
William H Aisenberg, Jessie Huang, Wanqu Zhu, Premraj Rajkumar, Randy Cruz, Lakshmi Santhanam, Niranjana Natarajan, Hwan Mee Yong, Breann De Santiago, Jung Jin Oh, A-Rum Yoon, Reynold A Panettieri, Oliver Homann, John K Sullivan, Stephen B Liggett, Jennifer L Pluznick, Steven S An
Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27894297/pulmonary-hypertension-and-vascular-remodeling-in-mice-exposed-to-crystalline-silica
#6
Igor N Zelko, Jianxin Zhu, Jeffrey D Ritzenthaler, Jesse Roman
BACKGROUND: Occupational and environmental exposure to crystalline silica may lead to the development of silicosis, which is characterized by inflammation and progressive fibrosis. A substantial number of patients diagnosed with silicosis develop pulmonary hypertension. Pulmonary hypertension associated with silicosis and with related restrictive lung diseases significantly reduces survival in affected subjects. An animal model of silicosis has been described previously however, the magnitude of vascular remodeling and hemodynamic effects of inhaled silica are largely unknown...
November 28, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27893716/hic-5-remodeling-of-the-stromal-matrix-promotes-breast-tumor-progression
#7
G J Goreczny, J L Ouderkirk-Pecone, E C Olson, M Krendel, C E Turner
The remodeling of the stromal extracellular matrix (ECM) has a crucial, but incompletely understood role during tumor progression and metastasis. Hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in breast tumor progression in vivo, Hic-5(-/-) mice were generated and crossed with the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic-5(-/-);PyMT mice exhibited increased latency and reduced growth, with fewer lung metastases, as compared with Hic-5(+/-);PyMT mice...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27891773/cigarette-smoke-alters-the-secretome-of-lung-epithelial-cells
#8
Alessandra Mossina, Christina Lukas, Juliane Merl-Pham, Franziska E Uhl, Kathrin Mutze, Andrea Schamberger, Claudia Staab-Weijnitz, Jie Jia, Ali Ö Yildirim, Melanie Königshoff, Stefanie M Hauck, Oliver Eickelberg, Silke Meiners
Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Many of its more than 4500 chemicals are highly reactive thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative mass spectrometry to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar-derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix (ECM) organization...
November 28, 2016: Proteomics
https://www.readbyqxmd.com/read/27888991/pulmonary-function-and-adverse-cardiovascular-outcomes-can-cardiac-function-explain-the-link
#9
Melissa S Burroughs Peña, Allison Dunning, Phillip J Schulte, Michael T Durheim, Peter Kussin, William Checkley, Eric J Velazquez
BACKGROUND: The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. METHODS: This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation...
December 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27887617/increased-expression-of-trop2-in-airway-basal-cells-potentially-contributes-to-airway-remodeling-in-chronic-obstructive-pulmonary-disease
#10
Qixiao Liu, Haijun Li, Qin Wang, Yuke Zhang, Wei Wang, Shuang Dou, Wei Xiao
BACKGROUND: The airway epithelium of chronic obstructive pulmonary disease (COPD) patients undergoes aberrant repair and remodeling after repetitive injury following exposure to environmental factors. Abnormal airway regeneration observed in COPD is thought to originate in the stem/progenitor cells of the airway epithelium, the basal cells (BCs). However, the molecular mechanisms underlying these changes remain unknown. Here, trophoblast cell surface antigen 2 (TROP2), a protein implicated in the regulation of stem cell activity, was examined in lung tissue samples from COPD patients...
November 25, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27886850/cellular-senescence-and-autophagy-in-the-pathogenesis-of-chronic-obstructive-pulmonary-disease-copd-and-idiopathic-pulmonary-fibrosis-ipf
#11
REVIEW
Kazuyoshi Kuwano, Jun Araya, Hiromichi Hara, Shunsuke Minagawa, Naoki Takasaka, Saburo Ito, Kenji Kobayashi, Katsutoshi Nakayama
Aging is associated with impairments in homeostasis. Although aging and senescence are not equivalent, the number of senescent cells increases with aging. Cellular senescence plays important roles in tissue repair or remodeling, as well as embryonic development. Autophagy is a process of lysosomal self-degradation that maintains a homeostatic balance between the synthesis, degradation, and recycling of cellular proteins. Autophagy diminishes with aging; additionally, accelerated aging can be attributed to reduced autophagy...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27886226/functional-improvement-and-regression-of-medial-hypertrophy-in-the-remodeled-pulmonary-artery-after-correction-of-systemic-left-to-right-shunt
#12
Chih-Hsin Hsu, Jun-Neng Roan, Jyh-Hong Chen, Chen-Fuh Lam
The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882343/proapoptotic-protein-bim-attenuates-estrogen-enhanced-survival-in-lymphangioleiomyomatosis
#13
Chenggang Li, Na Li, Xiaolei Liu, Erik Y Zhang, Yang Sun, Kouhei Masuda, Jing Li, Julia Sun, Tasha Morrison, Xiangke Li, Yuanguang Chen, Jiang Wang, Nagla A Karim, Yi Zhang, John Blenis, Mauricio J Reginato, Elizabeth P Henske, Jane J Yu
Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient-derived cells' resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27880037/suppressed-erythropoietin-expression-in-a-nitrofen-induced-congenital-diaphragmatic-hernia
#14
Hajime Takayasu, Koki Hagiwara, Kouji Masumoto
BACKGROUND: Erythropoietin (EPO), an essential stimulator of erythropoiesis produced by the fetal liver, is important both in vascular remodeling and modulation of the endothelial response in the pulmonary vasculature. In addition, EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct target of RA, and the retinoid pathway is altered in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. In the present study, we tested the hypothesis that the synthesis of EPO is suppressed in a rat model of CDH...
November 23, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27875656/involvement-of-jnk-in-tnf%C3%AE-driven-remodelling
#15
Irene Mj Eurlings, Niki L Reynaert, Cheryl van de Wetering, Scott W Aesif, Evi M Mercken, Rafael de Cabo, Jos L van der Velden, Yvonne M Janssen-Heininger, Emiel F M Wouters, Mieke A Dentener
Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested SPC-TNFα mice showed remodelling in alveolar and airway walls similar to what is observed in COPD patients...
November 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27873355/isoquercitrin-protects-against-pulmonary-hypertension-via-inhibiting-pasmcs-proliferation
#16
Yongtao Zhang, Yuqian Cui, Wei Deng, Hao Wang, Weidong Qin, Chengmin Huang, Chen Li, Jianning Zhang, Yuan Guo, Dawei Wu, Haipeng Guo
Pulmonary vascular remodeling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long-term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative, anti-inflammatory and anti-proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodeling in monocrotaline (MCT) induced PAH. Male Wistar rats were administered with vehicle or 0...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27873319/lung-neuroendocrine-tumours-deep-sequencing-of-the-four-who-histotypes-reveals-chromatin-remodelling-genes-as-major-players-and-a-prognostic-role-for-tert-rb1-men1-and-kmt2d
#17
Michele Simbolo, Andrea Mafficini, Katarzyna O Sikora, Matteo Fassan, Stefano Barbi, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Federica Grillo, Caterina Vicentini, Roberto Ferrara, Sara Pilotto, Federico Davini, Giuseppe Pelosi, Rita T Lawlor, Marco Chilosi, Giampaolo Tortora, Emilio Bria, Gabriella Fontanini, Marco Volante, Aldo Scarpa
Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNET) comprising the 4 WHO classification categories: 53 typical carcinoid (TC), 35 atypical carcinoid (AC), 27 large cell neuroendocrine carcinoma (LCNEC), and 33 small cell lung carcinoma (SCLC). A discovery screen was conducted on 46 samples using whole-exome sequencing and high-coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen and validated on additional 102 LNET by targeted NGS, and their prevalence was evaluated on the whole series...
November 22, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27871853/nur77-downregulation-triggers-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-in-mice-with-hypoxic-pulmonary-hypertension-via-the-axin2-%C3%AE-catenin-signaling-pathway
#18
Xiaowei Nie, Jianxin Tan, Youai Dai, Wenjun Mao, Yuan Chen, Guowei Qin, Guirong Li, Chenyou Shen, Jingjing Zhao, Jingyu Chen
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases...
November 15, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27871248/left-ventricle-remodeling-predicts-the-recurrence-of-ventricular-tachyarrhythmias-in-implantable-cardioverter-defibrillator-recipients-for-secondary-prevention
#19
Wei-Chieh Lee, Huang-Chung Chen, Yung-Lung Chen, Tzu-Hsien Tsai, Kuo-Li Pan, Yu-Sheng Lin, Mien-Cheng Chen
BACKGROUND: Implantable cardioverter defibrillator (ICD) is an effective treatment for secondary prevention of ventricular tachycardia/ventricular fibrillation (VT/VF). Left ventricular (LV) remodeling may develop before ICD implant and over time. However, it remains unclear how LV remodeling affects subsequent risk for recurrence VT/VF in ICD recipients under optimal medical therapy. METHODS: From May of 2004 to June of 2015, 144 patients received ICD implantation for secondary prevention were enrolled in this study...
November 21, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27864286/transforming-growth-factor-%C3%AE-plays-divergent-roles-in-modulating-vascular-remodeling-inflammation-and-pulmonary-fibrosis-in-a-murine-model-of-scleroderma
#20
Kazuyuki Tsujino, Nilgun Isik Reed, Amha Atakilit, Xin Ren, Dean Sheppard
The efficacy and feasibility of targeting TGF-β in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study, we analyzed how blocking TGF-β signaling affects pulmonary abnormalities in fos-related antigen 2 (Fra-2) transgenic mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGF-β signaling in the Fra-2 transgenic mice, we used a pan-TGF-β blocking antibody, 1D11, and transgenic mice in which TGF-β receptor type 2 (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-CreER; Tgfbr2flox/flox)...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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