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lung remodeling

Lisa R Young, Peter M Gulleman, Chelsi W Short, Harikrishna Tanjore, Taylor Sherrill, Aidong Qi, Andrew P McBride, Rinat Zaynagetdinov, John T Benjamin, William E Lawson, Sergey V Novitskiy, Timothy S Blackwell
Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC dysfunction and fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes pulmonary fibrosis in HPS, we investigated whether crosstalk between AECs and macrophages determines fibrotic susceptibility. We found that AECs from HPS mice produce excessive MCP-1, which was associated with increased macrophages in the lungs of unchallenged HPS mice...
October 20, 2016: JCI Insight
Milena V Oliveira, Soraia C Abreu, Gisele A Padilha, Nazareth N Rocha, Lígia A Maia, Christina M Takiya, Debora G Xisto, Bela Suki, Pedro L Silva, Patricia R M Rocco
Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0...
2016: Frontiers in Physiology
Haiying Chen, Hongli Yang, Hongmei Yue, Pádraig Michael Strappe, Peng Xia, Li Pan, Yingxin Zhang, Shoudong Chai, Shuangfeng Chen, Longle Ma, Lexin Wang
BACKGROUND: This study aimed to investigate the effect of bone marrow derived mesenchymal stem cells (rBMSCs) transduced with lentiviral vectors expressing endothelial nitric oxide synthase (eNOS) and/or a mutant caveolin-1(F92A-Cav1), on the pulmonary haemodynamics and structure in a rat model of pulmonary arterial hypertension (PAH). METHODS: Pulmonary arterial hypertension was induced with monocrotaline (MCT) in 60 adult male Wistar rats prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1, eNOS and/or F92A-Cav1...
September 9, 2016: Heart, Lung & Circulation
Arne O Melleby, Mari E Strand, Andreas Romaine, Kate M Herum, Biljana Skrbic, Christen P Dahl, Ivar Sjaastad, Arnt E Fiane, Jorge Filmus, Geir Christensen, Ida G Lunde
Pressure overload is a frequent cause of heart failure. Heart failure affects millions of patients worldwide and is a major cause of morbidity and mortality. Cell surface proteoglycans are emerging as molecular players in cardiac remodeling, and increased knowledge about their regulation and function is needed for improved understanding of cardiac pathogenesis. Here we investigated glypicans (GPC1-6), a family of evolutionary conserved heparan sulfate proteoglycans anchored to the extracellular leaflet of the cell membrane, in experimental and clinical heart failure, and explored the function of glypican-6 in cardiac cells in vitro...
2016: PloS One
Christine M Freeman, Jeffrey L Curtis
Hallmarks of chronic obstructive pulmonary disease (COPD) include innate inflammation and remodeling of small airways that begin in early disease and the development of lung lymphoid follicles (LLF), indicative of adaptive immunity, in more spirometrically-severe stages. Common to these processes in all stages is orchestration by dendritic cells (DC). Recently improved understanding of the analogous lung DC subsets in humans and mice has allowed for better integration and interpretation of the experimental and clinical pathological literature...
October 21, 2016: American Journal of Respiratory Cell and Molecular Biology
Namitosh Tyagi, D Dash, Rashmi Singh
OBJECTIVE: Paraquat (PQ), a potent herbicide can cause severe toxicity. We report here that fibroproliferation phase of acute lung injury (ALI) is initiated much earlier (within 48 h) after PQ intoxication than previously reported (after 2 weeks) and we aimed to study the protective effects of intranasal curcumin as new therapeutic strategy in mouse model. METHODS: Mice (Park's strain) were divided into five experimental groups (I) control, received only saline (0...
October 20, 2016: Inflammopharmacology
Joshua B Lewis, Dallin C Milner, Adam L Lewis, Todd M Dunaway, Kaleb M Egbert, Scott C Albright, Brigham J Merrell, Troy D Monson, Dallin S Broberg, Jason R Gassman, Daniel B Thomas, Juan A Arroyo, Paul R Reynolds
It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung...
October 17, 2016: International Journal of Environmental Research and Public Health
Sofia Sousa, Jorma Määttä
This overview addresses the recent research developments in the role of tumour-associated macrophages (TAM) in bone metastasis biology and management of breast and prostate cancer as well as in primary and lung metastatic osteosarcoma. Immunosuppressive M2-type TAMs have been shown to associate with poor prognosis. Throughout their life cycle, macrophages (Macs) can adapt to environmental cues and influence the surroundings by secreting different cytokines and enzymes crucial to matrix remodelling, infection fighting, immune regulation and/or inflammation...
September 2016: Journal of Bone Oncology
Nuria Roldan, Thomas K M Nyholm, J Peter Slotte, Jesús Pérez-Gil, Begoña García-Álvarez
To allow breathing and prevent alveolar collapse, lung surfactant (LS) develops a complex membranous system at the respiratory surface. LS is defined by a specific protein and lipid composition, including saturated and unsaturated phospholipid species and cholesterol. Surfactant protein C (SP-C) has been suggested to be an essential element for sustaining the presence of cholesterol in surfactant without functional impairment. In this work, we used a fluorescent sterol-partitioning assay to assess the effect of the surfactant proteins SP-B and SP-C on cholesterol distribution in membranes...
October 18, 2016: Biophysical Journal
Sharon L I Wong, Maria B Sukkar
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which regulates interactions between cells and their surrounding extracellular matrix (ECM), and thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair, and in the regulation of the immune response...
October 19, 2016: British Journal of Pharmacology
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
Jack R Staunton, Wilfred Vieira, King Leung Fung, Ross Lake, Alexus Devine, Kandice Tanner
One of the hallmarks of the malignant transformation of epithelial tissue is the modulation of stromal components of the microenvironment. In particular, aberrant extracellular matrix (ECM) remodeling and stiffening enhances tumor growth and survival and promotes metastasis. Type I collagen is one of the major ECM components. It serves as a scaffold protein in the stroma contributing to the tissue's mechanical properties, imparting tensile strength and rigidity to tissues such as those of the skin, tendons, and lungs...
September 2016: Cellular and Molecular Bioengineering
Anton H Schwabegger
Minimally invasive repair of pectus excavatum (MIRPE) or similar procedures for pectus excavatum (PE) repair, nowadays no longer performed by one single speciality, may not always achieve sufficient aesthetic results, particularly in the infrapectoral or infraxiphoidal region. Reasons for this include the diaphragm inhibiting correct positioning of the bars, as well as asymmetric deformities which may still be present after remodelling attempts. Furthermore, some cases develop a mild recurrence or partial concavity once the correction bar is removed...
September 2016: Annals of Cardiothoracic Surgery
Yuan Ma, Jia-Xiang Zhang, Ya-Nan Liu, Ai Ge, Hao Gu, Wang-Jian Zha, Xiao-Ning Zeng, Mao Huang
In the pathophysiology of asthma, structural cell dysfunction and concomitant microenvironment changes in airways are crucial to pathological progression, which involves oxidative stress. Caffeic acid phenethyl ester (CAPE) is an active anti-oxidative component obtained from propolis, and has been shown to have beneficial effects on several respiratory disorders, such as chronic obstructive pulmonary disease and lung cancer. However, the impact of CAPE on asthma is not well understood. Therefore, this study investigated the advantages of using CAPE to treat asthma and demonstrated the roles of CAPE in the regulation of airway microenvironments...
October 13, 2016: Free Radical Biology & Medicine
H Vroman, I M Bergen, B W S Li, J A C van Hulst, M Lukkes, D van Uden, R W Hendriks, M Kool
BACKGROUND: Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal center reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown...
October 15, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Christina Brandenberger, Christian Mühlfeld
Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth...
October 14, 2016: Cell and Tissue Research
Y S Prakash
Airway structure and function are key aspects of normal lung development, growth and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, COPD and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and finally, interactions with other airway cell types such as epithelium, fibroblasts and nerves...
October 14, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Yong Wang, Ting-Ting Ma, Na-Na Gao, Xiao-Ling Zhou, Jiang Hong, Rui Guo, Li-Na Jia, Hong Chang, Ying Gao, Zhi-Min Gao, Lei Pan
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL),which is a Chinese medicine rooted from traditional used herbs, has been used in clinic to treat cardiovascular and cerebrovascular diseases. However, it remains unknown whether TXL alleviates low pressure hypoxic pulmonary hypertension. AIM OF THE STUDY: Here, we aimed to observe the influence of TXL on pulmonary hypertension in a rat model that exposed to high altitude environment characterized by low pressure hypoxia...
October 10, 2016: Journal of Ethnopharmacology
Dalit Talmi-Frank, Zeev Altboum, Inna Solomonov, Yael Udi, Diego Adhemar Jaitin, Mordehay Klepfish, Eyal David, Alina Zhuravlev, Hadas Keren-Shaul, Deborah R Winter, Irit Gat-Viks, Michal Mandelboim, Tamar Ziv, Ido Amit, Irit Sagi
Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage...
October 12, 2016: Cell Host & Microbe
Andrew R Osterburg, Rebecca L Nelson, Benyamin Z Yaniv, Rachel Foot, Walter R F Donica, Madison A Nashu, Huan Liu, Kathryn A Wikenheiser-Brokamp, Joel Moss, Nishant Gupta, Francis X McCormack, Michael T Borchers
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that leads to progressive cyst formation and accelerated loss of pulmonary function. Neoplastic smooth muscle cells from an unknown source metastasize to the lung and drive destructive remodeling. Given the role of NK cells in immune surveillance, we postulated that NK cell activating receptors and their cognate ligands are involved in LAM pathogenesis. We found that ligands for the NKG2D activating receptor UL-16 binding protein 2 (ULBP2) and ULBP3 are localized in cystic LAM lesions and pulmonary nodules...
October 6, 2016: JCI Insight
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