BIOMAT Database Logo BIOMAT Database Logo

Transforming growth factor-β-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2. 2013

Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Department of Pharmacology, University of Melbourne, Grattan St., Parkville, Victoria 3010, Australia.

In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-β (TGF-β)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of human ASM cells after incubation with TGF-β (100 pM) and/or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and collagen remodeling. FGF-2 inhibited TGF-β-stimulated increases in transgelin (SM22) and calponin gene expression (n = 15, P < 0.01) in an extracellular signal-regulated kinase 1/2 (ERK1/2) signal transduction-dependent manner. The abundance of ordered α-smooth muscle actin (α-SMA) filaments formed in the presence of TGF-β were also reduced by FGF-2, as was the ratio of F-actin to G-actin (n = 8, P < 0.01). Furthermore, FGF-2 attenuated TGF-β-stimulated increases in ASM cell stiffness and the ASM-mediated contraction of lattices, composed of collagen fibrils (n = 5, P < 0.01). However, the TGF-β-stimulated production of IL-6 was not influenced by FGF-2 (n = 4, P > 0.05), suggesting that FGF-2 antagonism is selective for the regulation of ASM cell contractile protein expression, organization, and function. Another mitogen, thrombin (0.3 U ml(-1)), exerted no effect on TGF-β-regulated contractile protein expression (n = 8, P > 0.05), α-SMA organization, or the ratio of F-actin to G-actin (n = 4, P > 0.05), suggesting that the inhibitory effect of FGF-2 is dissociated from its mitogenic actions. The addition of FGF-2, 24 hours after TGF-β treatment, still reduced contractile protein expression, even when the TGF-β-receptor kinase inhibitor, SB431542 (10 μM), was added 1 hour before FGF-2. We conclude that the ASM cell differentiation promoted by TGF-β is antagonized by FGF-2. A better understanding of the mechanism of action for FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma.

UI MeSH Term Description Entries
D008840 Microfilament Proteins Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell. Actin Binding Protein,Actin-Binding Protein,Actin-Binding Proteins,Microfilament Protein,Actin Binding Proteins,Binding Protein, Actin,Protein, Actin Binding,Protein, Actin-Binding,Protein, Microfilament,Proteins, Actin-Binding,Proteins, Microfilament
D009124 Muscle Proteins The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN. Muscle Protein,Protein, Muscle,Proteins, Muscle
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D012137 Respiratory System The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. Respiratory Tract,Respiratory Systems,Respiratory Tracts,System, Respiratory,Tract, Respiratory
D002135 Calcium-Binding Proteins Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS. Calcium Binding Protein,Calcium-Binding Protein,Calcium Binding Proteins,Binding Protein, Calcium,Binding Proteins, Calcium,Protein, Calcium Binding,Protein, Calcium-Binding
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D003285 Contractile Proteins Proteins which participate in contractile processes. They include MUSCLE PROTEINS as well as those found in other cells and tissues. In the latter, these proteins participate in localized contractile events in the cytoplasm, in motile activity, and in cell aggregation phenomena. Contractile Protein,Protein, Contractile,Proteins, Contractile
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Transforming growth factor-beta1 in asthmatic airway smooth muscle enlargement: is fibroblast growth factor-2 required?
May 2010, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Transforming growth factor-β and smooth muscle differentiation.
March 2012, World journal of biological chemistry,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Cell division cycle 7 is a novel regulator of transforming growth factor-β-induced smooth muscle cell differentiation.
February 2012, The Journal of biological chemistry,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Transforming growth factor beta 1 inhibits mitogen-activated protein kinase induced by basic fibroblast growth factor in smooth muscle cells.
May 1996, The Biochemical journal,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor.
May 1991, Proceedings of the National Academy of Sciences of the United States of America,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Olfactomedin 2, a novel regulator for transforming growth factor-β-induced smooth muscle differentiation of human embryonic stem cell-derived mesenchymal cells.
December 2014, Molecular biology of the cell,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Fibroblast growth factor 9 signaling inhibits airway smooth muscle differentiation in mouse lung.
January 2009, Developmental dynamics : an official publication of the American Association of Anatomists,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Transforming growth factor-β and nuclear factor E2–related factor 2 regulate antioxidant responses in airway smooth muscle cells: role in asthma.
October 2011, American journal of respiratory and critical care medicine,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
Transforming growth factor-beta induces airway smooth muscle hypertrophy.
February 2006, American journal of respiratory cell and molecular biology,
Michael Schuliga, and Aqeel Javeed, and Trudi Harris, and Yuxiu Xia, and Chengxue Qin, and Zhexing Wang, and Xuehua Zhang, and Peter V S Lee, and Blanca Camoretti-Mercado, and Alastair G Stewart
BET bromodomains regulate transforming growth factor-β-induced proliferation and cytokine release in asthmatic airway smooth muscle.
April 2015, The Journal of biological chemistry,
Copied contents to your clipboard!