Proliferative Vascular Smooth Muscle Cells Stimulate Extracellular Matrix Production via Osteopontin/p38 MAPK Signaling Pathway. 2021

Huawei Pei, and Haiyue Zhang, and Chuan Tian, and Xiaogang Sun, and Xiangyang Qian, and Yanhai Meng, and Xiaobo Guo, and Qian Chang
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

BACKGROUND Extracellular matrix disorder and cellular phenotype transformation are the major histopathological features associated with ascending aortic aneurysms. Rare studies have investigated the relationship between cellular phenotype transformation and the abnormalities of the matrix constituents. In this study, we investigated whether the cellular phenotype transformation resulted in the extracellular matrix disorder. METHODS Aortic samples were obtained from 20 patients undergoing operations for ascending aortic aneurysms. Control aortic samples were obtained from 15 patients who underwent coronary artery bypass graft. The protein levels of osteopontin (OPN), collagen, and elastin were examined using Western blot, and quantitative reverse transcriptase-PCR was used to analyze the mRNA expression of collagen and elastin. In vitro experiment, vascular smooth muscle cells (VSMCs) were treated with recombinant human OPN (rh-OPN) or p38 MAPK inhibitor (SB203580) to investigate whether OPN and p38 MAPK regulated the expression of collagen and elastin. RESULTS The protein level of OPN and collagen III increased in ascending aortic aneurysm samples, compared with controls (p < 0.05). There was no difference in the protein level of elastin between aneurysm tissues and the controls. VSMCs treated with rh-OPN increased the collagen III and elastin protein level and mRNA expression (p < 0.05). Cells treated with SB203580 decreased the collagen III and elastin protein level and mRNA expression (p < 0.05). Furthermore, VSMCs incubated with SB203580 reduced the rh-OPN-induced production of collagen III and elastin (p < 0.05). CONCLUSIONS OPN, the proliferative VSMCs maker, increased the expression of extracellular matrix. OPN/p38 MAPK signaling pathways may protect against ascending aortic aneurysm progression.

UI MeSH Term Description Entries
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
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
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
D048051 p38 Mitogen-Activated Protein Kinases A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens. Mitogen-Activated Protein Kinase p38,p38 Mitogen-Activated Protein Kinase,p38 MAP Kinase,p38 MAPK,p38 Protein Kinase,p38 SAPK,MAP Kinase, p38,MAPK, p38,Mitogen Activated Protein Kinase p38,Protein Kinase, p38,p38 Mitogen Activated Protein Kinase,p38 Mitogen Activated Protein Kinases
D053495 Osteopontin A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3. Bone Sialoprotein 1,Bone Sialoprotein I,Secreted Phosphoprotein 1,Sialoprotein 1,Uropontin,Sialoprotein 1, Bone,Sialoprotein I, Bone
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

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