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Fgf tgf lung

Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
Aurélien Justet, Audrey Joannes, Valérie Besnard, Joëlle Marchal-Sommé, Madeleine Jaillet, Phillippe Bonniaud, Jean-Michel Sallenave, Brigitte Solhonne, Yves Castier, Pierre Mordant, Hervé Mal, Aurélie Cazes, Raphael Borie, Arnaud A Mailleux, Bruno Crestani
Fibroblast Growth Factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both Human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (Adcont) was performed...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ryota Kurimoto, Takahiro Ebata, Shunichiro Iwasawa, Tsukasa Ishiwata, Yuji Tada, Koichiro Tatsumi, Yuichi Takiguchi
The epithelial-to-mesenchymal transition (EMT) in cancer is associated with invasion, metastasis and chemoresistance. Recent studies have revealed the increased expression of programmed death-ligand 1 (PD-L1) in cells undergoing EMT. The underlying mechanism of EMT involves transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2). Pirfenidone and the known EMT-suppressor nintedanib suppress pulmonary fibrosis partially through suppression of TGF-β. The present study aimed to determine whether pirfenidone has the potential to induce EMT-reversion, using nintedanib as a reference...
July 2017: Oncology Letters
Fang Liu, Shasha Song, Zhi Yi, Min Zhang, Jiali Li, Fang Yang, Hongtao Yin, Xiufeng Yu, Chao Guan, Ying Liu, Zizhen Liu, Jing Wang, Daling Zhu
The epithelial-to-mesenchymal transition (EMT) is a crucial event during non-small-cell lung cancer (NSCLC) invasion and metastasis. However, the mechanisms involved in NSCLC EMT have not been fully clarified. Hepatocyte growth factor (HGF) and human biliverdin reductase (hBVR) are reported to contribute to EMT in several diseases. Here, we show that compared with transforming growth factor beta (TGF-β), fibroblast growth factor (FGF), and epidermal growth factor (EGF), HGF is an important cell factor for EMT in NSCLC cell lines A549 and H460...
May 26, 2017: European Journal of Pharmacology
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
April 28, 2017: Oncotarget
Zhi Ao, Shilong Yu, Pin Qian, Wenhong Gao, Ruiling Guo, Xiaoxiao Dong, Jianping Xu, Ruijie Zhang, Chaowen Jiang, Fuyun Ji, Guisheng Qian
Fibromodulin (FMOD), an ECM small leucine-rich proteoglycan (SLRP), was reported to promote angiogenesis not only during wound healing, but also in optical and cutaneous angiogenesis-dependent diseases. However, whether it plays important roles in tumor angiogenesis remains unclear. To explore the role of FMOD in tumor angiogenesis of human small cell lung cancer (SCLC), initially the study analyzed the relationship of FMOD expression in cancer tissues of SCLC with clinical characteristics. The analysis revealed that the positive FMOD expression was significantly associated with extensive stage of SCLC and higher vascular density...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Diptiman Chanda, Ashish Kurundkar, Sunad Rangarajan, Morgan Locy, Karen Bernard, Nirmal S Sharma, Naomi J Logsdon, Hui Liu, David K Crossman, Jeffrey C Horowitz, Stijn De Langhe, Victor J Thannickal
Cellular plasticity and de-differentiation are hallmarks of tissue/organ regenerative capacity in diverse species. Despite a more restricted capacity for regeneration, humans with age-related chronic diseases, such as cancer and fibrosis, show evidence of a recapitulation of developmental gene programs. We have previously identified a resident population of mesenchymal stromal cells (MSCs) in the terminal airways-alveoli by bronchoalveolar lavage (BAL) of human adult lungs. In this study, we characterized MSCs from BAL of patients with stable and progressive idiopathic pulmonary fibrosis (IPF), defined as <5% and ≥10% decline, respectively, in forced vital capacity over the preceding 6-month period...
November 21, 2016: Scientific Reports
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...
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
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