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Fgf smooth muscle

Pei-Yu Chen, Lingfeng Qin, Guangxin Li, George Tellides, Michael Simons
Smooth muscle cells (SMCs) in normal blood vessels exist in a highly differentiate state characterized by expression of SMC-specific contractile proteins ("contractile phenotype"). Following blood vessel injury in vivo or when cultured in vitro in the presence of multiple growth factors, SMC undergo a phenotype switch characterized by the loss of contractile markers and appearance of expression of non-muscle proteins ("proliferative phenotype"). While a number of factors have been reported to modulate this process, its regulation remains uncertain...
2016: Scientific Reports
Takehiro Nakahara, Keiko Kawai-Kowase, Hiroki Matsui, Hiroaki Sunaga, Toshihiro Utsugi, Tatsuya Iso, Masashi Arai, Shouichi Tomono, Masahiko Kurabayashi
BACKGROUND AND AIMS: Elevated fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular mortality in patients with chronic kidney disease. However, both clinical and basic research have demonstrated conflicting evidence regarding the pathophysiological role of FGF23 in vascular calcification. The aim of this study was to determine the role of FGF23 in the osteoblastic gene expression in vascular smooth muscle cells (SMCs). METHODS AND RESULTS: We transduce human aortic SMCs (HASMCs) expressing klotho and FGF receptors with the adenovirus expressing human FGF23 (Ad-FGF23)...
October 2016: Atherosclerosis
Xue Liu, Yuanjian Chen, Cody W McCoy, Tieqiang Zhao, Darryl L Quarles, Min Pi, Syamal K Bhattacharya, Gwendalyn King, Yao Sun
BACKGROUND: Soluble Klotho functions as an endocrine factor that plays important roles in a variety of pathophysiological processes. Soluble Klotho contains 130 KDa and 65 KDa isoforms. However, their distinct individual functional heterogeneity remains uncertain. Herein, we investigated the regulatory role of two soluble Klothos on cardiac fibrogenic responses. METHODS AND RESULTS: The effect of soluble Klothos on myofibroblast differentiation, proliferation, and collagen synthesis/degradation were examined in cultured mouse cardiac myofibroblasts...
October 2016: American Journal of Hypertension
Sun-Hwa Song, Kyungjong Kim, Eun-Kyung Jo, Young-Wook Kim, Jin-Sook Kwon, Sun Sik Bae, Jong-Hyuk Sung, Sang Gyu Park, Jee Taek Kim, Wonhee Suh
OBJECTIVE: Vascular smooth muscle cells (VSMCs) modulate their phenotype between synthetic and contractile states in response to environmental changes; this modulation plays a crucial role in the pathogenesis of restenosis and atherosclerosis. Here, we identified fibroblast growth factor 12 (FGF12) as a novel key regulator of the VSMC phenotype switch. APPROACH AND RESULTS: Using murine models and human specimens, we found that FGF12 was highly expressed in contractile VSMCs of normal vessel walls but was downregulated in synthetic VSMCs from injured and atherosclerotic vessels...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
E Peterová, A Mrkvicová, L Podmolíková, M Řezáčová, J Kanta
Rat liver myofibroblasts (MFB) are the key cells involved in the deposition of extracellular matrix in fibrotic liver. They were isolated by repeated passaging of non-parenchymal cell fraction and cultured in 3-dimensional (3D) collagen gel mimicking tissue. The transfer of MFB from plastic dishes to collagen resulted in the change in their shape from large and spread to slender with long extensions. The expression of transforming growth factor-beta1 (TGF-beta1) and of MFB markers, alpha-smooth muscle actin (alpha-SMA) and cellular fibronectin (EDA-FN), on protein level was significantly decreased in collagen gel...
July 15, 2016: Physiological Research
Pei-Yu Chen, Lingfeng Qin, Guangxin Li, George Tellides, Michael Simons
The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFβ signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFβ signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFβ activity, thereby promoting smooth muscle differentiation and decreasing proliferation...
2016: EMBO Molecular Medicine
Luis Cezar Farias de Oliveira, Taís Marolato Danilucci, Antonio Hernandes Chaves-Neto, Ana Paula Campanelli, Tereza Cristina Cardoso da Silva, Sandra Helena Penha Oliveira
The aim of this study was to evaluate the mechanism involved in the stem cell factor (SCF)-induced production of fibroblast growth factor-2 (FGF-2), transforming growth factor-β1 (TGF-β1), and chemokine (C-C motif) ligand 3 (CCL3) in tracheal smooth muscle cells (tSMCs) and the signaling pathway involved in the process. tSMC primary cultures were stimulated with SCF and evaluated at 24 h. Cells treated with specific antibodies did not show any immunolabeling for cytokeratin or fibroblast activation protein, but were positive for α-smooth muscle actin, indicating the purity of the primary cell line...
June 2016: Journal of Interferon & Cytokine Research
Björn Hegner, Theres Schaub, Rusan Catar, Angelika Kusch, Philine Wagner, Kirill Essin, Claudia Lange, Gabriela Riemekasten, Duska Dragun
INTRODUCTION: Obliterative vasculopathy and fibrosis are hallmarks of systemic sclerosis (SSc), a severe systemic autoimmune disease. Bone marrow-derived mesenchymal stromal cells (MSCs) from SSc patients may harbor disease-specific abnormalities. We hypothesized disturbed vascular smooth muscle cell (VSMC) differentiation with increased propensity towards myofibroblast differentiation in response to SSc-microenvironment defining growth factors and determined responsible mechanisms. METHODS: We studied responses of multipotent MSCs from SSc-patients (SSc-MSCs) and healthy controls (H-MSCs) to long-term exposure to CTGF, b-FGF, PDGF-BB or TGF-β1...
2016: PloS One
I Blaas, K Heinz, P Würtinger, A Türkcan, C Tepeköylü, M Grimm, C Doppler, K Danzl, B Messner, D Bernhard
UNLABELLED: Essentials Vein graft failure is the most frequent late onset complication of coronary artery bypass grafting. Cuff technique-based interposition mouse model including new anticoagulation regime was conducted. Early vein graft thrombi may serve as a niche for smooth muscle cell colonization. The focal character of early thrombi may form the basis for the asymmetry of intimal hyperplasia. SUMMARY: Background Autologous saphenous veins are widely used in coronary artery bypass grafting; however, 10 years after surgery, 40% of grafts are completely occluded, and another 30% show reduced blood flow...
May 2016: Journal of Thrombosis and Haemostasis: JTH
Zechun Kang, Yunxia Ji, Guanghua Zhang, Yubei Qu, Liang Zhang, Wanglin Jiang
AIMS: An abnormal ratio of vasohibin-2/vasohibin-1 may be involved in the abnormal angiogenesis and vascular remodeling during pulmonary arterial hypertension (PAH). MAIN METHODS: To evaluate the pharmacological actions of Ponatinib (AP) in experimental model of PAH, the effects of AP on TGF-β1-mediated endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMEC), and the hypoxic human pulmonary artery smooth muscle cells (HPASMC) proliferation and HPMEC in vitro, and on bleomycin (BLM)-induced PAH in vivo were investigated...
March 1, 2016: Life Sciences
Vladislav S Baranov, Tatyana E Ivaschenko, Maria I Yarmolinskaya
Endometriosis (EM) and uterine leiomyoma (UL) are two most frequent benign tumors of monoclonal origin affecting about 30% of all women in their reproductive age. Modern molecular technologies have made a tremendous impact in understanding both disorders. Here is the first comparative analysis of molecular mechanisms underlying development of EM and UL as it looks from the platform of systems genetics. Similarities and differences of EM and UL at their incipient stages are enlightened with special emphasis on their gene networks, gene expression, and epigenetic regulation, of pathologic development...
April 2016: Systems Biology in Reproductive Medicine
Bethany N Smith, Neil A Bhowmick
Epithelial-mesenchymal transition (EMT) is a complex molecular program that regulates changes in cell morphology and function during embryogenesis and tissue development. EMT also contributes to tumor progression and metastasis. Cells undergoing EMT expand out of and degrade the surrounding microenvironment to subsequently migrate from the primary site. The mesenchymal phenotype observed in fibroblasts is specifically important based on the expression of smooth muscle actin (α-SMA), fibroblast growth factor (FGF), fibroblast-specific protein-1 (FSP1), and collagen to enhance EMT...
2016: Journal of Clinical Medicine
Dinender Singla, Jing Wang
We hypothesized that fibroblast growth factor-9 (FGF-9) would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p < 0.05). Additionally, the number of c-kit(+ve)/SM α-actin(+ve) cells and c-kit(+ve)/CD31(+ve) cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p < 0...
2016: Oxidative Medicine and Cellular Longevity
Pengfei Xu, Yingjie Zhang, Yunye Liu, Qingyan Yuan, Liying Song, Mingyao Liu, Zhihang Liu, Yongbi Yang, Junyan Li, Deshan Li, Guiping Ren
Fibroblast growth factor 21 (FGF-21) is a secreted protein, which has anti-diabetic and lipocaic effects, but its ability to protect against hepatic fibrosis has not been studied. In this study, we investigated the ability of FGF-21 to attenuate dimethylnitrosamine (DMN)-induced hepatic fibrogenesis in mice and the mechanism of its action. Hepatic fibrosis was induced by injection of DMN, FGF-21 was administered to the mice once daily in association with DMN injection till the end of the experiment. Histopathological examination, tissue 4-hydroxyproline content and expressions of smooth muscle α-actin (α-SMA) and collagen I were measured to assess hepatic fibrosis...
January 1, 2016: Toxicology and Applied Pharmacology
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
Luc A J Roelofs, Egbert Oosterwijk, Barbara B M Kortmann, Willeke F Daamen, Dorien M Tiemessen, Katrien M Brouwer, Alex J Eggink, A Jane Crevels, Rene M H Wijnen, Toin H van Kuppevelt, Paul J Geutjes, Wout F J Feitz
Tissue engineering may become an alternative to current bladder augmentation techniques. Large scaffolds are needed for clinically significant augmentation, but can result in fibrosis and graft shrinkage. The purpose of this study was to investigate whether smart acellular collagen-heparin scaffolds with growth factors (GFs) VEGF, FGF2, and HB-EGF enhance bladder tissue regeneration and bladder capacity in a large animal model of diseased bladder. Scaffolds of bovine type I collagen with heparin and VEGF, FGF2, and HB-EGF measuring 3...
January 2016: Tissue Engineering. Part A
Sook Kyoung Kim, Jaeyeon Lee, Myeongjin Song, Mirim Kim, Soon Jung Hwang, Hwanseok Jang, Yongdoo Park
Combinations of angiogenic growth factors have been shown to have synergistic effects on angiogenesis and natural wound healing in various animal models. Each growth factor has unique roles during angiogenesis; vascular endothelial growth factor (VEGF) plays a key role during the initial step of angiogenesis, whereas PDGF functions in the maturation of blood vessels. We used a combination of three angiogenic growth factors to increase angiogenesis in vitro and in vivo. We chose VEGF as a basic factor and added platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) to induce angiogenesis in three in vitro and in vivo models: 3D angiogenesis assay, 3D co-culture, and matrigel plug implantation assay...
August 13, 2015: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
BreAnne MacKenzie, Martina Korfei, Ingrid Henneke, Zaneta Sibinska, Xia Tian, Stefanie Hezel, Salma Dilai, Roxana Wasnick, Beate Schneider, Jochen Wilhelm, Elie El Agha, Walter Klepetko, Werner Seeger, Ralph Schermuly, Andreas Günther, Saverio Bellusci
BACKGROUND: Recent clinical studies show that tyrosine kinase inhibitors slow the rate of lung function decline and decrease the number of acute exacerbations in patients with Idiopathic Pulmonary Fibrosis (IPF). However, in the murine bleomycin model of fibrosis, not all tyrosine kinase signaling is detrimental. Exogenous ligands Fibroblast Growth Factor (FGF) 7 and 10 improve murine lung repair and increase survival after injury via tyrosine kinase FGF receptor 2b-signaling. Therefore, the level and location of FGF/FGFR expression as well as the exogenous effect of the most highly expressed FGFR2b ligand, FGF1, was analyzed on human lung fibroblasts...
2015: Respiratory Research
Michael Schuliga, Simon G Royce, Shenna Langenbach, Asres Berhan, Trudi Harris, Christine R Keenan, Alastair G Stewart
During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). FXa may have an important role in asthma, being involved in thrombin activation and an agonist of protease-activated receptor-1 (PAR-1). Extracellular annexin A2 and integrins are also implicated in PAR-1 signaling. In this study, the potential role of PAR-1 in mediating the effects of FXa on human airway smooth muscle (ASM) cell cytokine production and proliferation was investigated. FXa (5-50 nM), but not FX, stimulated increases in ASM IL-6 production and cell number after 24- and 48-hour incubation, respectively (P < 0...
February 2016: American Journal of Respiratory Cell and Molecular Biology
K G Battiston, R S Labow, C A Simmons, J P Santerre
UNLABELLED: Despite the importance of immune cells in regulating the wound healing process following injury, there are few examples of synthetic biomaterials that have the capacity to push the body's immune cells toward pro-regeneration phenotypes, and fewer still that are designed with the intention of achieving this immunomodulatory character. While monocytes and their derived macrophages have been recognized as important contributors to tissue remodeling in vivo, this is primarily believed to be due to their ability to regulate other cell types...
September 2015: Acta Biomaterialia
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