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Fgf lung remodeling

Elie El Agha, Felix Schwind, Clemens Ruppert, Andreas Günther, Saverio Bellusci, Ralph Theo Schermuly, Djuro Kosanovic
Idiopathic pulmonary arterial hypertension (IPAH), pulmonary hypertension (PH) due to lung disease and/or hypoxia and idiopathic pulmonary fibrosis (IPF) are increasingly recognized as important contributors to mortality and morbidity worldwide. Among others, the current treatment paradigm considers broad inhibition of receptor tyrosine kinases, a strategy that likely leads to collateral inhibition of signaling pathways that are critical for lung repair and regeneration. Fibroblast growth factor 7 (FGF7) and FGF10 signaling in the lung through FGF receptor 2 (FGFR2) are involved in epithelial cell protection and renewal, and mutations in their corresponding genes in humans are linked to increased susceptibility to lung pathologies such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Heather L Menden, Sheng Xia, Sherry M Mabry, Angels Navarro, Michael F Nyp, Venkatesh Sampath
In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsis-induced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)-mediated inflammation and alveolar remodeling. Six-day-old NOX2+/+ and NOX2-/- mice were injected with intraperitoneal LPS to induce sepsis...
December 2016: American Journal of Respiratory Cell and Molecular Biology
Audrey Joannes, Stéphanie Brayer, Valérie Besnard, Joëlle Marchal-Sommé, Madeleine Jaillet, Pierre Mordant, Hervé Mal, Raphael Borie, Bruno Crestani, Arnaud A Mailleux
Idiopathic pulmonary fibrosis (IPF) is characterized by an accumulation of extracellular matrix proteins and fibroblasts in the distal airways. Key developmental lung signaling pathways are reactivated in IPF. For instance, fibroblast growth factor 9 (FGF9) and FGF18, involved in epithelial-mesenchymal interactions, are critical for lung development. We evaluated the expression of FGF9, FGF18, and FGF receptors (FGFRs) in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration, and differentiation of control and IPF human lung fibroblasts (HLFs)...
April 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Yaguo Zheng, Hong Ma, Enci Hu, Zhiwei Huang, Xiaoling Cheng, Changming Xiong
BACKGROUND: Numerous studies have demonstrated that fibroblast growth factor-2 (FGF-2) signaling may play a pivotal role in the development of pulmonary arterial hypertension (PAH). Excessive endothelial FGF-2 contributes to smooth muscle hyperplasia and disease progression. PD173074 is a potent FGF receptor 1 (FGFR-1) inhibitor that displays high activity and selectivity. The aim of this study was to investigate the effects of PD173074 on monocrotaline-induced PAH. We also evaluated whether FGFR-1 inhibition could attenuate bone morphogenetic protein type II receptor (BMPR-II) downregulation in the monocrotaline model...
November 2015: Journal of Cardiovascular Pharmacology
Jordi Ruiz-Camp, Rory E Morty
Lung fibroblasts play a key role in postnatal lung development, namely, the formation of the alveolar gas exchange units, through the process of secondary septation. Although evidence initially highlighted roles for fibroblasts in the production and remodeling of the lung extracellular matrix, more recent studies have described the presence of different fibroblast subsets in the developing lung. These subsets include myofibroblasts and lipofibroblasts and their precursors. These cells are believed to play different roles in alveologenesis and are localized to different regions of the developing septa...
October 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Xiao Na Ge, Sung Gil Ha, Amrita Rao, Yana G Greenberg, Muaz Nik Rushdi, Jeffrey D Esko, Savita P Rao, P Sriramarao
Heparan sulfate (HS) proteoglycans (HSPGs) participate in several aspects of inflammation because of their ability to bind to growth factors, chemokines, interleukins and extracellular matrix proteins as well as promote inflammatory cell trafficking and migration. We investigated whether HSPGs play a role in the development of airway remodeling during chronic allergic asthma using mice deficient in endothelial- and leukocyte-expressed N-deacetylase/N-sulfotransferase-1 (Ndst1), an enzyme involved in modification reactions during HS biosynthesis...
August 2014: Glycobiology
Nicolas Ricard, Ly Tu, Morane Le Hiress, Alice Huertas, Carole Phan, Raphaël Thuillet, Caroline Sattler, Elie Fadel, Andrei Seferian, David Montani, Peter Dorfmüller, Marc Humbert, Christophe Guignabert
BACKGROUND: Pericytes and their crosstalk with endothelial cells are critical for the development of a functional microvasculature and vascular remodeling. It is also known that pulmonary endothelial dysfunction is intertwined with the initiation and progression of pulmonary arterial hypertension (PAH). We hypothesized that pulmonary endothelial dysfunction, characterized by abnormal fibroblast growth factor-2 and interleukin-6 signaling, leads to abnormal microvascular pericyte coverage causing pulmonary arterial medial thickening...
April 15, 2014: Circulation
Johannes Trebing, Isabell Lang, Martin Chopra, Steffen Salzmann, Mahan Moshir, Karen Silence, Simone S Riedel, Daniela Siegmund, Andreas Beilhack, Christoph Otto, Harald Wajant
Expression of fibroblast growth factor (FGF)-inducible 14 (Fn14), a member of the tumor necrosis factor receptor superfamily, is typically low in healthy adult organisms, but strong Fn14 expression is induced in tissue injury and tissue remodeling. High Fn14 expression is also observed in solid tumors, which is why this receptor is under consideration as a therapeutic target in oncology. Here, we describe various novel mouse-human cross-reactive llama-derived recombinant Fn14-specific antibodies (5B6, 18D1, 4G5) harboring the human IgG1 Fc domain...
January 2014: MAbs
Andrew Makanya, Aikaterini Anagnostopoulou, Valentin Djonov
During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways that form the prospective gas exchanging chambers, where a thin blood-gas barrier (BGB) is established. In the mammalian lung, this proceeds through conversion of type II cells to type I cells, thinning, and elongation of the cells as well as extrusion of the lamellar bodies. Subsequent diminution of interstitial tissue and apposition of capillaries to the alveolar epithelium establish a thin BGB...
2013: BioMed Research International
S Kunzmann, J J P Collins, E Kuypers, A W Gavilanes, B W Kramer
The developing lung and immune systems are very plastic and their developmental pathway can be influenced by various endogenous and/or exogenous factors. In the last years translational research with various animal models has been helpful to answer some basic questions about the effect of chorioamnionitis on maturation and development of the foetal lung and immune system. Chorioamnionitis can induce a cascade of lung injury, pulmonary inflammation and remodelling in the foetal lung. Chorioamnionitis-induced IL-1 production is consistently associated with lung maturation, induced by enhancing surfactant protein and lipid synthesis...
August 2012: Zeitschrift Für Geburtshilfe und Neonatologie
Amrita Dosanjh
The fibroblast growth factor (FGF) signaling pathway is integral to the pathogenesis of many airway diseases and in the growth and development of the normal lung. The FGF pathway has a role in key regulatory pathways of fibrosis, and provides a number of potential therapeutic targets for future research.
March 2012: Journal of Interferon & Cytokine Research
Nikos Sgantzis, Anthie Yiakouvaki, Eumorphia Remboutsika, Dimitris L Kontoyiannis
Lung development is controlled by regulatory networks governing mesenchymal-epithelial interactions. Transcription factors and signaling molecules are known to participate in this process, yet little is known about the post-transcriptional regulation of these networks. Here we demonstrate that the RNA-binding protein (RBP) HuR is an essential regulator of mesenchymal responses during lung branching. Its epiblast-induced deletion blocked the morphogenesis of distal bronchial branches at the initiation of the pseudoglandular stage...
June 15, 2011: Developmental Biology
Hye Young Yum, Jae Youn Cho, Marina Miller, David H Broide
BACKGROUND: Basic fibroblast growth factor (bFGF) is a cytokine that is mitogenic for fibroblasts and smooth muscle and may play a role in airway remodeling in asthma. We have used a mouse model of chronic ovalbumin (OVA) allergen-induced airway remodeling to determine whether bFGF and fibroblast growth factor receptor-1 are expressed and regulated by corticosteroids in the airway, as well as to determine whether bFGF mediates expression of another proremodeling cytokine, transforming growth factor (TGF)-β1...
2011: International Archives of Allergy and Immunology
Danny Jonigk, Katharina Theophile, Kais Hussein, Oliver Bock, Ulrich Lehmann, Clemens L Bockmeyer, Jens Gottlieb, Stefan Fischer, Andre Simon, Tobias Welte, Lavinia Maegel, Hans Kreipe, Florian Laenger
Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far. Obliterated and unremodelled airways from explanted lungs (n = 19) from patients suffering from chronic allograft dysfunction, infection, graft-versus-host disease and toxic exposure were isolated by laser-assisted microdissection...
September 2010: Virchows Archiv: An International Journal of Pathology
Michael J Evans, Michelle V Fanucchi, Charles G Plopper, Dallas M Hyde
The basement membrane zone (BMZ) appears as three component layers: the lamina lucida, lamina densa, and lamina reticularis. The laminas lucida and densa are present during all stages of development. The lamina reticularis appears during postnatal development. Collagens I, III, and V form heterogeneous fibers that account for the thickness of the lamina reticularis. Additionally, there are three proteoglycans considered as integral components of the BMZ: perlecan, collagen XVIII, and bamacan. Perlecan is the predominant heparan sulfate proteoglycan in the airway BMZ...
June 2010: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Carlos Ramos, Carina Becerril, Martha Montaño, Carolina García-De-Alba, Remedios Ramírez, Marco Checa, Annie Pardo, Moisés Selman
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the expansion of the fibroblast/myofibroblast population and aberrant remodeling. However, the origin of mesenchymal cells in this disorder is still under debate. Recent evidence indicates that epithelial-mesenchymal transition (EMT) induced primarily by TGF-beta1 plays an important role; however, studies regarding the opposite process, mesenchymal-epithelial transition, are scanty. We have previously shown that fibroblast growth factor-1 (FGF-1) inhibits several profibrogenic effects of TGF-beta1...
August 2010: American Journal of Physiology. Lung Cellular and Molecular Physiology
Wei Shi, Felicia Chen, Wellington V Cardoso
Chronic obstructive pulmonary disease (COPD) results in major remodeling of the distal airspaces and changes in the differentiation profile of the airway epithelium. The cellular and molecular mechanisms involved in initiation and progression of this disease are little understood. Although environmental factors, including cigarette smoke, have been directly implicated in the pathogenesis of COPD, genetic risk factors also appear to play a fundamental role in the individual's susceptibility to this disease. Lung development depends on precise coordination of signals, such as fibroblast growth factors (Fgf), Sonic Hedgehog (Shh), retinoic acid, Notch, and Tgf beta...
December 1, 2009: Proceedings of the American Thoracic Society
Mohamed Izikki, Christophe Guignabert, Elie Fadel, Marc Humbert, Ly Tu, Patricia Zadigue, Philippe Dartevelle, Gerald Simonneau, Serge Adnot, Bernard Maitre, Bernadette Raffestin, Saadia Eddahibi
Pulmonary hypertension (PH) is a progressive, lethal lung disease characterized by pulmonary artery SMC (PA-SMC) hyperplasia leading to right-sided heart failure. Molecular events originating in pulmonary ECs (P-ECs) may contribute to the PA-SMC hyperplasia in PH. Thus, we exposed cultured human PA-SMC to medium conditioned by P-EC from patients with idiopathic PH (IPH) or controls and found that IPH P-EC-conditioned medium increased PA-SMC proliferation more than control P-EC medium. Levels of FGF2 were increased in the medium of IPH P-ECs over controls, while there was no detectable difference in TGF-beta1, PDGF-BB, or EGF levels...
March 2009: Journal of Clinical Investigation
S Tourdot, S Mathie, T Hussell, L Edwards, H Wang, P J M Openshaw, J Schwarze, C M Lloyd
BACKGROUND: The mechanisms underlying exacerbation of asthma induced by respiratory syncytial virus (RSV) infection have been extensively studied in human and animal models. However, most of these studies focused on acute inflammation and little is known of its long-term consequences on remodelling of the airway tissue. OBJECTIVE: The aim of the study was to use a murine model of prolonged allergen-induced airway inflammation to investigate the effect of RSV infection on allergic airway inflammation and tissue remodelling...
June 2008: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Hui Zou, Xiu-hong Nie, Yi Zhang, Mu Hu, Yu Alex Zhang
BACKGROUND: Proliferation, cell migration and phenotypic modulation of airway smooth muscle cells (ASMCs) are important features of airway remodelling in asthma. The precise cellular and molecular mechanisms that regulate ASMCs proliferation, migration and phenotypic modulation in the lung remain unknown. Basic fibroblast growth factor (bFGF), a highly specific chemotactic and mitogenic factor for many cell types, appears to be involved in the development of airway remodelling. Our study assessed whether bFGF directly stimulates the proliferation, migration and phenotypic modulation of ASMCs...
March 5, 2008: Chinese Medical Journal
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