Biomaterial Database

Dexmedetomidine represses TGF-β1-induced extracellular matrix production and proliferation of airway smooth muscle cells by inhibiting MAPK signaling pathway. 2022

Rong Zhou, and Xiaoyan Chen

Department of Anesthesiology, Rugao Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, China.

BACKGROUND Airway remodeling is implicated in the pathogenesis of asthma, and abnormal proliferation of airway smooth muscle cells (ASMCs) contribute to airway remodeling. Inflammatory mediator, transforming growth factor-β1 (TGF-β1), stimulates the proliferation of ASMCs, and is associated with airway remodeling in asthma. Dexmedetomidine (DEX) has been widely used in the adjuvant therapy of acute asthma. OBJECTIVE The potential effects of DEX on extracellular matrix (ECM) production and proliferation of ASMCs were investigated in this study. METHODS Human ASMCs were incubated with TGF-β1 for 48 hours, and then treated with different concentrations of DEX for another 24 hours. Cell proliferation was detected by MTT and BrdU (5'-bromo-2'-deoxyuridine) staining. Flow cytometry was used to assess cell apoptosis, and western blot was applied to identify the underlying mechanism. RESULTS TGF-β1 induced increase in cell viability and bromodeoxyuridine (BrdU) positive cells in ASMCs while repressed cell apoptosis. Second, TGF-β1-induced ASMCs were then treated with different concentrations of DEX. Cell viability of TGF-β1-induced ASMCs was decreased by incubation of DEX. The number of BrdU positive cells in TGF-β1-induced ASMCs was reduced by incubation of DEX. Moreover, incubation of DEX promoted cell apoptosis of TGF-β1-induced ASMCs. Third, incubation of DEX attenuated TGF-β1-induced increase in fibronectin, collagen I, MMP9, and versican in ASMCs. Lastly, the up-regulation of phosphorylated extracellular receptor kinase (p-ERK), phosphorylated Jun N-terminal Kinase (p-JNK), and p-p38 in TGF-β1-induced ASMCs was reversed by incubation of DEX. CONCLUSIONS DEX suppressed TGF-β1-induced ECM production and proliferation of ASMCs through inactivation of p38 mitogen-activated protein kinase (MAPK) pathway, providing a potential strategy for prevention of asthma.

UI	MeSH Term	Description	Entries
D005109	Extracellular Matrix	A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.	Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D049109	Cell Proliferation	All of the processes involved in increasing CELL NUMBER including CELL DIVISION.	Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D053773	Transforming Growth Factor beta1	A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.	TGF-beta1,Transforming Growth Factor-beta1,TGF-beta-1,TGF-beta1 Latency-Associated Protein,TGF-beta1LAP,Transforming Growth Factor beta 1 Latency Associated Peptide,Transforming Growth Factor beta I,Latency-Associated Protein, TGF-beta1,TGF beta 1,TGF beta1 Latency Associated Protein,TGF beta1LAP
D056151	Airway Remodeling	The structural changes in the number, mass, size and/or composition of the airway tissues.	Airway Remodelling,Asthmatic Airway Remodeling,Asthmatic Airway Remodelling,Asthmatic Airway Wall Remodeling,Asthmatic Airway Wall Remodelling,Small Airway Remodeling,Small Airway Remodelling,Airway Wall Remodelling,Airway Remodeling, Asthmatic,Airway Remodeling, Small,Airway Remodelings,Airway Remodelings, Asthmatic,Airway Remodelings, Small,Airway Remodelling, Asthmatic,Airway Remodelling, Small,Airway Remodellings,Airway Remodellings, Asthmatic,Airway Remodellings, Small,Airway Wall Remodellings,Asthmatic Airway Remodelings,Asthmatic Airway Remodellings,Remodeling, Airway,Remodeling, Asthmatic Airway,Remodeling, Small Airway,Remodelings, Airway,Remodelings, Asthmatic Airway,Remodelings, Small Airway,Remodelling, Airway,Remodelling, Airway Wall,Remodelling, Asthmatic Airway,Remodelling, Small Airway,Remodellings, Airway,Remodellings, Airway Wall,Remodellings, Asthmatic Airway,Remodellings, Small Airway,Small Airway Remodelings,Small Airway Remodellings,Wall Remodelling, Airway,Wall Remodellings, Airway
D020927	Dexmedetomidine	An imidazole derivative that is an agonist of ADRENERGIC ALPHA-2 RECEPTORS. It is closely related to MEDETOMIDINE, which is the racemic form of this compound.	Cepedex,Dexdomitor,Dexdor,Igalmi,Sedadex,Sileo,Dexmedetomidine Hydrochloride,MPV-1440,Precedex,Hydrochloride, Dexmedetomidine,MPV 1440,MPV1440
D020928	Mitogen-Activated Protein Kinases	A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).	Mitogen Activated Protein Kinase,Mitogen-Activated Protein Kinase,Kinase, Mitogen-Activated Protein,Kinases, Mitogen-Activated Protein,Mitogen Activated Protein Kinases,Protein Kinase, Mitogen-Activated,Protein Kinases, Mitogen-Activated
D032389	Myocytes, Smooth Muscle	Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).	Smooth Muscle Cells,Cell, Smooth Muscle,Cells, Smooth Muscle,Myocyte, Smooth Muscle,Smooth Muscle Cell,Smooth Muscle Myocyte,Smooth Muscle Myocytes