Add to Favorites. In addition to association with the appropriate cyclin, CDKs require dephosphorylation of inhibitory phosphorylation sites for activation (, Specific inhibitors can also regulate the activity of CDK 4 and CDK 2. The observation that CDKs 4 and 2 were not activated despite the expression of cyclin D and cyclin E prompted us to examine the expression of Cdc25A and CDK inhibitors. The present study examined the activation of extracellular signal-regulated kinase (ERK) signaling as well as the expression and activity of cell cycle proteins in FGF2-stimulated intimal smooth muscle cells. In smooth muscle cells, the immediate action of endothelin is to trigger vasoconstriction (vasospasm), and its long-term effect is to promote cellular proliferation , . Avril V. Somlyo, Marion J. Siegman, in Muscle, 2012 Introduction. Smooth muscle proliferation in hypertensive vascular disease again results in increased wall mass and a narrowed lumen. Blood vessel injury increases growth factor secretion and matrix synthesis, which promotes SMC proliferation and neointimal hyperplasia via FAK (focal adhesion kinase). December 14, To verify that the infused FGF2 is able to bind to and activate its receptor in intimal smooth muscle cells, we measured the activation of the ERK signaling pathway. In these same arteries, high levels of the cyclin-dependent kinase inhibitors p27, Male Harlan Sprague-Dawley rats (Tyler Laboratories, Bellevue, Washington), age 3–3.5 months, were used throughout these experiments. Track Citations. Persistent epithelial damage may result in the release of platelet-derived growth factor (PDGF), which stimulates smooth muscle proliferation, followed by fibroblastic proliferation. The control of vascular cell proliferation is complex and encompasses interactions of many regulatory molecules and signaling … Herein, we recapitulated the importance of signaling cascades relevant for the regulation of vascular cell proliferation. The mechanism in which external factors stimulate growth and rearrangement is not yet fully understood. Abnormal vascular smooth muscle cell (VSMC) proliferation is involved in restenosis following percutaneous transluminal angioplasty (PTCA) and accelerated arteriosclerosis after cardiac transplantation. Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. https://doi.org/10.1016/j.biotechadv.2018.04.006. Abstract. Epub 2004 Nov 11. Detailed understanding of the mechanism underlying this process is essential for the identification of new lead compounds (e.g., natural products) for vascular therapies. Though vascular smooth muscle cell (VSMC) proliferation underlies all cardiovascular hyperplastic disorders, our understanding of the molecular mechanisms responsible for this cellular process is still incomplete. MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY, ATTENUATION OF BASIC FIBROBLAST GROWTH FACTOR 2-STIMULATED PROLIFERATION IS ASSOCIATED WITH INCREASED EXPRESSION OF CELL CYCLE INHIBITORS*, Cell Type-specific E2F Activation and Cell Cycle Progression Induced by the Oncogene Product Tax of Human T-cell Leukemia Virus Type I*, Sodium Channel β Subunits Mediate Homophilic Cell Adhesion and Recruit Ankyrin to Points of Cell-Cell Contact*, Quantification of Smooth Muscle Cell Proliferation, Response of Arterial Smooth Muscle Cell to Exogenous FGF2, FGF2 Stimulation of Cytoplasmic Signaling Pathways, Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0), We use cookies to help provide and enhance our service and tailor content and ads. Our data would support the conclusion that FGF2 stimulates prolonged activation of ERKs 1/2 as well as activation of PI 3-kinase and that this activation is similar to that seen in acutely injured medial smooth muscle cell stimulated with FGF2. This procedure completely removes the endothelial cells lining the carotid artery and yet causes only a small increase (1.5%) in medial smooth muscle cell proliferation (. 55 year old man with paratesticular mass (Arch Pathol Lab Med 2003;127:E111) 55 year old man with smooth muscle hyperplasia of epididymis (J Surg Case Rep 2011;2011:10) 66 year old man with simultaneous leiomyoma and contralateral smooth muscle hyperplasia of epididymis (Pathologica 2009;101:119) Complex multilocular cystic lesion of rete testis, accompanied by smooth muscle … In order to study which factors control the growth of these cells, we and many others have used a model of smooth muscle cell proliferation induced by mechanical injury of the rat carotid artery (, FGF2 signal transduction involves the activation of many different cytoplasmic signaling molecules, including the extracellular signal-regulated kinases 1 and 2 (ERKs 1 and 2) (, Although FGF2 stimulation requires activation of cytoplasmic signaling molecules such as the ERKs and PI 3-kinase to induce proliferation, the resultant signaling must ultimately lead to activation of the cyclin-dependent kinases (CDKs) in order for cells to progress through the G, Although the expression of the cyclins are necessary for activation of the CDKs, they are not sufficient; there are specific CDK inhibitors capable of inhibiting the CDKs even in the presence of the cyclins (, Our data show that FGF2 stimulation of smooth muscle cells in established intimal lesions activates both the ERKs and PI 3-kinase and increases cyclin D expression but does not lead to phosphorylation of the retinoblastoma protein, activation of CDK 2, or increased expression of cyclin A. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. Advanced glycation end products (AGEs) have been widely regarded as an important inducing factor in the pathogenesis of diabetic arteriosclerosis, and the proliferation and migration of vascular smooth muscle cells (VSMCs) are also involved in this process. Copyright © 2021 Elsevier B.V. or its licensors or contributors. FGF2 stimulation, however, did not lead to phosphorylation of the retinoblastoma protein (Rb), CDK 2 activation, or expression of cyclin A. The frozen tissue was then ground with mortar and pestle under liquid nitrogen until reduced to a fine powder, which was suspended in a cell lysis solution containing 10 m, Equal amounts of protein from carotid arteries prepared for Western blot analysis were electrophoresed on a 10% SDS-polyacrylamide gel containing 0.4 mg/ml myelin basic protein. The small vessel change is though to be etiologic of the increased peripheral resistance of high blood pressure. At least four cross-sections per carotid were quantitated. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Vascular smooth muscle cell proliferation as a therapeutic target. Asthma; bronchi; proliferation; remodelling; smooth muscle; Asthma is a chronic inflammatory disease, characterised by the association of bronchial hyperresponsiveness, inflammation and remodelling 1–3.Current medications are effective in treating acute airway narrowing and decreasing inflammation but are relatively less effective in preventing chronic structural changes 4. The expression of cyclins D and E, however, was not sufficient to induce a high level of proliferation, and we hypothesize that high levels of p15, Received in revised form: By continuing you agree to the Use of Cookies. The phosphatase Cdc25A is required for the activation of CDK 4 and CDK 2, while CDK inhibitors inhibit the activity of CDKs 4 and 2 in the presence of the cyclins. FGF2 activates ERKs 1 and 2, and Western blot analysis showed that cyclin D, cyclin E, and cyclin-dependent kinase (CDKs) 2 and 4 were expressed in intimal smooth muscle cells after FGF2 infusion. O. Recently, endothelial TWIST1 has been linked to pulmonary hypertension (PH) and endothelial-to-mesenchymal transition, yet the role of TWIST1 in smooth muscle cells (SMCs) remains so far unclear. DOI: https://doi.org/10.1074/jbc.275.15.11270. It reported that Long noncoding BRAF-activated noncoding RNA (BANCR) and miR-34c played opposite roles in the regulation of the proliferation of VSMCs, indicating that there might be a potential interaction between them. Aberrant vascular smooth muscle cell (VSMCs) proliferation involves in the development of atherosclerosis. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. LDLs and growth factors stimulate smooth muscle proliferation as well arterial from NMNC 1235 at Central New Mexico Community College Tel. Thus, the present study aims to examine the anti-vasoconstrictory and anti-proliferatory effects of cilostazol in … © 2018 Elsevier Inc. All rights reserved. All rights reserved. Excessive proliferation of vascular smooth muscle cells contributes to the etiology of such diseases, including atherosclerosis, restenosis, and pulmonary hypertension. 38 SRF binds to cis DNA regulatory elements called CArG boxes (CC(A/T-rich) 6 GG), which are found in the promoters of muscle-specific genes, as well as serum-inducible genes such as c-fos that regulate proliferation. Smooth muscle cell proliferation was measured by counting the number of labeled nuclei, and the [ 3 H]thymidine index ((labeled nuclei/total nuclei) × 100%) was calculated. Falcetti E(1), Hall SM, Phillips PG, Patel J, Morrell NW, Haworth SG, Clapp LH. The feature of PH is intense remodeling of small pulmonary arteries by myofibroblast and smooth muscle cell proliferation, and for familial pulmonary arterial hypertension, the bone morphogenetic protein type II receptor (BMPR-II) mutation in pulmonary artery smooth muscle cells contributes to abnormal growth responses to the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) [ 5 Pertinent to these findings are data linking PI 3-kinase (, There are several possible explanations for the increased expression of p27, This work shows that FGF2 is weakly mitogenic for smooth muscle cells in intimal lesions. Rationale: The bHLH (basic helix-loop-helix) transcription factor TWIST1 (Twist-related protein 1) controls cell proliferation and differentiation in tissue development and disease processes. 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