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Fgf tgf lung

Chiko Shimbori, Pierre-Simon Bellaye, Jiaji Xia, Jack Gauldie, Kjetil Ask, Carlos Ramos, Carina Becerril, Annie Pardo, Moises Selman, Martin Kolb
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibroblast and myofibroblast proliferation, and extensive deposition of extracellular matrix (ECM). Fibroblast growth factor-1 (FGF-1) belongs to the FGF family and has been shown to inhibit fibroblast collagen production and differentiation into myofibroblasts, and revert epithelial-mesenchymal transition by inhibiting TGF-β1 signalling pathways. However, the precise role of FGF-1 in pulmonary fibrosis has not yet been elucidated. In this study, we explore the mechanisms underlying the anti-fibrogenic effect of FGF-1 in pulmonary fibrosis in vitro and in vivo by prolonged transient overexpression of FGF-1 (AdFGF-1) and TGF-β1 (AdTGF-β1) using adenoviral vectors...
October 2016: Journal of Pathology
Sharad Kumar Suthar, Manu Sharma
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the widely used medications all over the world, indicated for pain, fever, and inflammation. It is now well established that inflammation and cancer are closely linked with each other. Inflammatory mediators, like cyclooxygenase (COX), vascular endothelial growth factor (VEGF), tumor growth factor (TGF), fibroblast growth factor (FGF), chemokines, and cytokines and related genes, such as inhibitor of nuclear factor-kappa B kinase (IKK) and nuclear factor-kappa B (NF-κB) have been shown to be up-regulated in various cancers...
April 28, 2016: Mini Reviews in Medicinal Chemistry
Xiang Chen, Chaowen Shi, Xiannan Meng, Kaijia Zhang, Xiaoyao Li, Cong Wang, Zou Xiang, Kebin Hu, Xiaodong Han
Pulmonary fibrosis is a progressive lung disorder of unknown etiology, which is characterized by alterations in alveolar epithelium function, fibroblast activation, and increased extracellular matrix deposition. Recent studies have demonstrated that PF is associated with uncontrolled production of cytokines after lung injury. In the present study, we found that transforming growth factor-β1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) were both upregulated in bleomycin-induced fibrotic lung tissue and primary murine alveolar epithelial Type II (ATII) cells treated with bleomycin...
August 2016: Experimental and Molecular Pathology
Hasan Şimşek, Şeniz Demiryürek, Tuncer Demir, Hüsne Didem Atabay, Ali Osman Çeribasi, Recep Bayraktar, Davut Sinan Kaplan, Serdar Öztuzcu, Beyhan Cengiz
OBJECTIVES: Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue's life...
February 2016: Iranian Journal of Basic Medical Sciences
Yubei Qu, Guanghua Zhang, Yunxia Ji, Haibo Zhua, Changjun Lv, Wanglin Jiang
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. The treatment options for IPF are very limited. Gambogic acid (GA) has anticancer effect and anti-proliferative activity which is extracted from a dried yellow resin of the Garcinia hanburyi Hook.f. [Clusiaceae (Guttiferae)] in Southeast Asia. However, the anti-fibrotic activities of GA have not been previously investigated. METHODS: In this study, the effects of GA on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells and endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMECs), on the proliferation of human lung fibroblasts (HLF-1) were investigated in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo...
April 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ryota Kurimoto, Shunichiro Iwasawa, Takahiro Ebata, Tsukasa Ishiwata, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Shuhei Koide, Atsushi Iwama, Yuichi Takiguchi
Epithelial-to-mesenchymal transition (EMT) is a malignant cancer phenotype characterized by augmented invasion and metastasis, chemoresistance, and escape from host-immunity. This study sought to identify efficient methods for inducing EMT reversion, to evaluate alterations in chemosensitivity and immune-protectiveness, and to elucidate the underlying mechanisms. In this study, the human lung adenocarcinoma cell lines PC-9 and HCC-827, harboring an EGFR mutation, were treated with TGF-β and FGF-2 to induce EMT...
May 2016: International Journal of Oncology
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
Hiba Qari, Aya Hamao-Sakamoto, Clay Fuselier, Yi-Shing Lisa Cheng, Harvey Kessler, John Wright
Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm that secretes fibroblast growth factor-23 (FGF-23) and causes oncogenic osteomalacia. It occurs in adults with equal gender distribution and the most common location is the lower extremities, followed by the head and neck. Besides osteomalacia, the clinical presentation includes bone pain and multiple bone fractures. Microscopic features consist of spindle cells, multinucleated giant cells, and calcifications embedded in a chondromyxoid matrix. Laboratory findings indicate normal calcium and parathyroid levels, hypophosphatemia, and increased levels of FGF-23 that usually revert to normal after surgical removal...
June 2016: Head and Neck Pathology
Jing Bai, Ting-Yuan Tu, Choong Kim, Jean Paul Thiery, Roger D Kamm
Experiments were performed in a modified microfluidic platform recapitulating part of the in vivo tumor microenvironment by co-culturing carcinoma cell aggregates embedded in a three-dimensional (3D) collagen scaffold with human umbilical vein endothelial cells (HUVECs). HUVECs were seeded in one channel of the device to initiate vessel-like structures in vitro prior to introducing the aggregates. The lung adenocarcinoma cell line A549 and the bladder carcinoma cell line T24 were tested. Dose-response assays of four drugs known to interfere with Epithelial Mesenchymal Transition (EMT) signaling pathways were quantified using relative dispersion as a metric of EMT progression...
November 3, 2015: Oncotarget
Yubei Qu, Liang Zhang, Zechun Kang, Wanglin Jiang, Changjun Lv
TGF-β1/Smad3 pathway plays a key role in the pathogenesis of idiopathic pulmonary fibrosis, including lung fibroblasts proliferation and epithelial cell aberrant activation. Ponatinib is a multi-targeted tyrosine-kinase inhibitor. However, whether Ponatinib has anti-fibrotic functions is unknown. In this study, the effects of Ponatinib on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1), on the apoptosis of human type I alveolar epithelial cells (AT I) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo...
October 2015: Pulmonary Pharmacology & Therapeutics
Bettina Oehrle, Gerald Burgstaller, Martin Irmler, Stefan Dehmel, Jessica Grün, Tiffany Hwang, Susanne Krauss-Etschmann, Johannes Beckers, Silke Meiners, Oliver Eickelberg
The invasion of activated fibroblasts represents a key pathomechanism in fibrotic diseases, carcinogenesis and metastasis. Invading fibroblasts contribute to fibrotic extracellular matrix (ECM) formation and the initiation, progression, or resistance of cancer. To construct transcriptome-wide signatures of fibroblast invasion, we used a multiplex phenotypic 3D invasion assay using lung fibroblasts. Microarray-based gene expression profiles of invading and non-invading fibroblasts demonstrated that 1,049 genes were differentially regulated (>1...
2015: Scientific Reports
Grazia Graziani, Pedro M Lacal
Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that acts as a co-receptor for various members of the vascular endothelial growth factor (VEGF) family. Its ability to bind or modulate the activity of a number of other extracellular ligands, such as class 3 semaphorins, TGF-β, HGF, FGF, and PDGF, has suggested the involvement of NRP-1 in a variety of physiological and pathological processes. Actually, this co-receptor has been implicated in axon guidance, angiogenesis, and immune responses. NRP-1 is also expressed in a variety of cancers (prostate, lung, pancreatic, or colon carcinoma, melanoma, astrocytoma, glioblastoma, and neuroblastoma), suggesting a critical role in tumor progression...
2015: Frontiers in Oncology
Sarah X L Huang, Michael D Green, Ana Toste de Carvalho, Melanie Mumau, Ya-Wen Chen, Sunita L D'Souza, Hans-Willem Snoeck
Lung and airway epithelial cells generated in vitro from human pluripotent stem cells (hPSCs) have applications in regenerative medicine, modeling of lung disease, drug screening and studies of human lung development. Here we describe a strategy for directed differentiation of hPSCs into developmental lung progenitors, and their subsequent differentiation into predominantly distal lung epithelial cells. The protocol entails four stages that recapitulate lung development, and it takes ∼50 d. First, definitive endoderm (DE) is induced in the presence of high concentrations of activin A...
March 2015: Nature Protocols
Liang Zhang, Yunxia Ji, Zechun Kang, Changjun Lv, Wanglin Jiang
An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated...
February 15, 2015: Toxicology and Applied Pharmacology
Saima Charni Chaabane, Alexandra Coomans de Brachène, Ahmed Essaghir, Amélie Velghe, Sandra Lo Re, Julie Stockis, Sophie Lucas, Levon M Khachigian, François Huaux, Jean-Baptiste Demoulin
Transforming growth factor-β (TGFβ) is a key mediator of fibrogenesis. TGFβ is overexpressed and activated in fibrotic diseases, regulates fibroblast differentiation into myofibroblasts and induces extracellular matrix deposition. Platelet-derived growth factor (PDGF) is also a regulator of fibrogenesis. Some studies showed a link between TGFβ and PDGF in certain fibrotic diseases. TGFβ induces PDGF receptor alpha expression in scleroderma fibroblasts. PDGF-C and -D are the most recently discovered ligands and also play a role in fibrosis...
2014: PloS One
Xueyan Peng, Meagan W Moore, Hong Peng, Huanxing Sun, Ye Gan, Robert J Homer, Erica L Herzog
Pulmonary fibrosis is a difficult to treat, often fatal disease whose pathogenesis involves dysregulated TGF-β1 signaling. CD4+CD25+FoxP3+ Regulatory T cells ("Tregs") exert important effects on host tolerance and arise from naïve CD4+ lymphocytes in response to TGF-β1. However, the precise contribution of Tregs to experimentally induced murine lung fibrosis remains unclear. We sought to better understand the role of Tregs in this context. Using a model of fibrosis caused by lung specific, doxycycline inducible overexpression of the bioactive form of the human TGF-β1 gene we find that Tregs accumulate in the lung parenchyma within 5 days of transgene activation and that this enhancement persists to at least 14 days...
2014: Frontiers in Pharmacology
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
Michael P Lisanti, Aristotelis Tsirigos, Stephanos Pavlides, Kimberley Jayne Reeves, Maria Peiris-Pagès, Amy L Chadwick, Rosa Sanchez-Alvarez, Rebecca Lamb, Anthony Howell, Ubaldo E Martinez-Outschoorn, Federica Sotgia
Mammography is an important screening modality for the early detection of DCIS and breast cancer lesions. More specifically, high mammographic density is associated with an increased risk of breast cancer. However, the biological processes underlying this phenomenon remain largely unknown. Here, we re-interrogated genome-wide transcriptional profiling data obtained from low-density (LD) mammary fibroblasts (n = 6 patients) and high-density (HD) mammary fibroblasts (n = 7 patients) derived from a series of 13 female patients...
2014: Cell Cycle
Katy M Roach, Katy Morgan Roach, Stephen Mark Duffy, William Coward, Carol Feghali-Bostwick, Heike Wulff, Peter Bradding
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a common, progressive and invariably lethal interstitial lung disease with no effective therapy. We hypothesised that K(Ca)3.1 K(+) channel-dependent cell processes contribute to IPF pathophysiology. METHODS: K(Ca)3.1 expression in primary human lung myofibroblasts was examined using RT-PCR, western blot, immunofluorescence and patch-clamp electrophysiology. The role of K(Ca)3.1 channels in myofibroblast proliferation, wound healing, collagen secretion and contraction was examined using two specific and distinct K(Ca)3...
2013: PloS One
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