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Kou-gi Shyu - One of the best experts on this subject based on the ideXlab platform.
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Mechanical Stretch via transforming growth factor β1 activates microrna208a to regulate endoglin expression in cultured rat cardiac myoblasts
European Journal of Heart Failure, 2013Co-Authors: Kou-gi Shyu, Bao Wei Wang, Chiu Mei Lin, Hang ChangAbstract:Aims MicroRNAs (miRNAs) play a role in cardiac remodelling. MiR208a is essential for the expression of the genes involved in cardiac hypertrophy and fibrosis. The mechanism of regulation of miR208a involved in cardiac hypertrophy by Mechanical stress is still unclear. We sought to investigate the mechanism of regulation of miR208a and the target gene of miR208a in cardiac cells by Mechanical Stretch. Methods and results Rat H9c2 cells (cardiac myoblasts) grown on a flexible membrane base were Stretched via vacuum to 20% of maximum elongation at 60 cycles/min. Mechanical Stretch significantly enhanced miR208a expression after 4 h of Stretch. Exogenous addition of transforming growth factor-β1 (TGF-β1) increased miR208a expression, and pre-treatment with TGF-β1 antibody attenuated the miR208a expression induced by Stretch. Mechanical Stretch significantly increased endoglin and collagen I expression for 6–24 h. Exogenous addition of TGF-β1 and overexpression of miR208a up-regulated endoglin and collagen I expression, while antagomir208a and Smad3/4 inhibitor attenuated endoglin and collagen I expression induced by Stretch. Mechanical Stretch and TGF-β1 increased Smad3/4–DNA binding activity and miR208a promoter activity, and TGF-β1 antibody and Smad3/4 inhibitor decreased the Smad3/4–DNA binding activity and miR208a promoter activity induced by Stretch. Conclusion Cyclic Mechanical Stretch enhances miR208a expression in cultured rat cardiac myoblasts. The Stretch-induced miR208a is mediated by TGF-β1. Mir208a activates endoglin expression and may result in cardiac fibrosis.
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Cellular and Molecular Effects of Mechanical Stretch on Vascular Cells
Mechanosensitivity and Mechanotransduction, 2010Co-Authors: Kou-gi ShyuAbstract:The vascular endothelium is a dynamic cellular interface between the vessel wall and the blood stream. It plays an important role by sensing the alterations in biological, chemical, and physical properties of blood flow to maintain homeostasis. Cells in the cardiovascular system are permanently subjected to Mechanical forces due to pulsatile nature of blood flow and shear stress, created by the beating hearts. These haemodynamic forces play an important role in the regulation of vascular development, remodeling, wound healing, atherosclerotic lesion formation, and endothelial progenitor cell function. Mechanical Stretch can modulate cell alignment and differentiation, migration, survival or apoptosis, vascular remodeling, and autocrine and paracrine functions in smooth muscle cells. Laminar shear stress exerts anti-apoptotic, anti-atherosclerotic, and anti-thrombotic effects on endothelial cells. However, low shear stress or high laminar shear stress exerts atherogenic effect on endothelial cells. Knowledge of the impact of Mechanical Stretch on the cardiovascular system is vital to the understanding of pathogenesis of cardiovascular diseases and is also crucial to provide new insights in the prevention and therapy of cardiovascular diseases.
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Cellular and molecular effects of Mechanical Stretch on vascular cells and cardiac myocytes.
Clinical science (London England : 1979), 2009Co-Authors: Kou-gi ShyuAbstract:Cells in the cardiovascular system are permanently subjected to Mechanical forces due to the pulsatile nature of blood flow and shear stress, created by the beating heart. These haemodynamic forces play an important role in the regulation of vascular development, remodelling, wound healing and atherosclerotic lesion formation. Mechanical Stretch can modulate several different cellular functions in VSMCs (vascular smooth muscle cells). These functions include, but are not limited to, cell alignment and differentiation, migration, survival or apoptosis, vascular remodelling, and autocrine and paracrine functions. Laminar shear stress exerts anti-apoptotic, anti-atherosclerotic and antithrombotic effects on ECs (endothelial cells). Mechanical Stretch of cardiac myocytes can modulate growth, apoptosis, electric remodelling, alterations in gene expression, and autocrine and paracrine effects. The aim of the present review is primarily to summarize the cellular and molecular effects of Mechanical Stretch on vascular cells and cardiac myocytes, emphasizing the molecular mechanisms underlying the regulation. Knowledge of the impact of Mechanical Stretch on the cardiovascular system is vital to the understanding of the pathogenesis of cardiovascular diseases, and is also crucial to provide new insights into the prevention and therapy of cardiovascular diseases.
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regulation of discoidin domain receptor 2 by cyclic Mechanical Stretch in cultured rat vascular smooth muscle cells
Hypertension, 2005Co-Authors: Kou-gi Shyu, Bao Wei Wang, Ya Meng Chao, Peiliang KuanAbstract:Discoidin domain receptor 2 (DDR2) plays potential roles in the regulation of collagen turnover mediated by smooth muscle cells in atherosclerosis. How Mechanical Stretch affects the regulation of ...
Guanbin Song - One of the best experts on this subject based on the ideXlab platform.
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rhoa rock cytoskeletal dynamics and focal adhesion kinase are required for Mechanical Stretch induced tenogenic differentiation of human mesenchymal stem cells
Journal of Cellular Physiology, 2012Co-Authors: Guanbin Song, Yuanhui Song, Sachi WatanabeAbstract:Human bone marrow mesenchymal stem cells (hMSCs) have the potential to differentiate into tendon/ligament-like lineages when they are subjected to Mechanical Stretching. However, the means through which Mechanical Stretch regulates the tenogenic differentiation of hMSCs remains unclear. This study examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion kinase (FAK) in Mechanical Stretch-induced tenogenic differentiation characterized by the up-regulation of tendon-related marker gene expression. Our findings showed that RhoA/ROCK and FAK regulated Mechanical Stretch-induced realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK and cytoskeletal organization were essential to Mechanical Stretch-activated FAK phosphorylation at Tyr397. We also demonstrated that this process can be blocked by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses Mechanical Stretching and drives Mechanical Stretch-induced tenogenic differentiation of hMSCs. This work provides novel insights regarding the mechanisms of tenogenesis in a Stretch-induced environment and supports the therapeutic potential of hMSCs.
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RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for Mechanical Stretch-induced tenogenic differentiation of human mesenchymal stem cells.
Journal of cellular physiology, 2012Co-Authors: Guanbin Song, Yuanhui Song, Sachi WatanabeAbstract:Human bone marrow mesenchymal stem cells (hMSCs) have the potential to differentiate into tendon/ligament-like lineages when they are subjected to Mechanical Stretching. However, the means through which Mechanical Stretch regulates the tenogenic differentiation of hMSCs remains unclear. This study examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion kinase (FAK) in Mechanical Stretch-induced tenogenic differentiation characterized by the up-regulation of tendon-related marker gene expression. Our findings showed that RhoA/ROCK and FAK regulated Mechanical Stretch-induced realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK and cytoskeletal organization were essential to Mechanical Stretch-activated FAK phosphorylation at Tyr397. We also demonstrated that this process can be blocked by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses Mechanical Stretching and drives Mechanical Stretch-induced tenogenic differentiation of hMSCs. This work provides novel insights regarding the mechanisms of tenogenesis in a Stretch-induced environment and supports the therapeutic potential of hMSCs.
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Mechanical Stretch-induced f-actin reorganization and tenogenic differentiation of human mesenchymal stem cells
2012Co-Authors: Guanbin SongAbstract:Human bone marrow mesenchymal stem cells (hMSCs) are multipotent adult stem cells which are capable of diverse lineages commitment and are considered as a promising cell source for various tissue repair and regeneration. It is well known that Mechanical stimuli regulate the biological functions of hMSCs. The purpose of this paper is to investigate the effect of Mechanical Stretch on cytoskeleton reorganization, gene and protein expressions of differentiation-related markers. Our findings showed that Mechanical Stretch induced f-actin reorganization, promoted the gene expressions of tendon-related markers including collagen type I (Col I), collagen type III (Col III), tenascin-C (TNC) and scleraxis (SCX), and decreased the gene expressions of collagen type II (Col II) and MSC-protein (MSC-p). Our studies also manifested that the protein expressions of Col I and TNC were increased, and the protein expression of Runx2 was inhibited by Mechanical Stretch. These results indicate that Mechanical Stretch may trigger the differentiation of hMSCs into tenocytes. This work provides novel insights into the differentiation of tenogenesis in a strain-induced environment and supports the therapeutic potential of hMSCs.
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Effect of Focal Adhesion Kinase on the Regulation of Realignment and Tenogenic Differentiation of Human Mesenchymal Stem Cells by Mechanical Stretch
Connective tissue research, 2011Co-Authors: Guanbin SongAbstract:Focal adhesion kinase (FAK) is a focal adhesion-associated protein kinase involved in cell adhesion and spreading. It is recruited as a participant in focal adhesion dynamics between cells and has a role in cell motility, differentiation, and survival. The role of FAK in the differentiation of human mesenchymal stem cells (hMSCs), however, is not well understood, particularly in terms of tenogenic differentiation. In this study, we reported that FAK regulates the Mechanical Stretch-induced realignment of hMSCs. We showed that FAK can be activated by Mechanical Stretch and, with a 10 μM PF 573228 (a novel small molecule inhibitor of FAK) treatment, FAK autophosphorylation at Tyr397 is significantly decreased. Moreover, our findings demonstrated that this decrease in FAK autophosphorylation at Tyr397 leads to the attenuation of upregulation of Mechanical Stretch-induced mRNA expression of tendon-related genes, including type I collagen, type III collagen, tenascin-C, and scleraxis. These results indicate that the FAK signaling molecule plays an important role in regulating cell realignment and tenogenic differentiation of hMSCs when induced by Mechanical Stretch. Collectively, our findings provide novel insight into the role of FAK in the realignment and mechanotransduction of hMSCs during the process of tenogenic differentiation induced by Mechanical Stretch.
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regulation of cyclic longitudinal Mechanical Stretch on proliferation of human bone marrow mesenchymal stem cells
Molecular & cellular biomechanics : MCB, 2007Co-Authors: Guanbin Song, Hitoshi Soyama, Toshiro Ohashi, Masaaki SatoAbstract:Mechanical stimulation is critical to both physiological and pathological states of living cells. Although a great deal of research has been done on biological and biochemical regulation of the behavior of bone marrow mesenchymal stem cells (MSCs), the influence of bioMechanical factors on their behavior is still not fully documented. In this study, we investigated the modulation of Mechanical Stretch magnitude, frequency, and duration on the human marrow mesenchymal stem cells (hMSCs) proliferation by an in vitro model system using a Mechanical Stretch loading apparatus, and optimized the Stretch regime for the proliferation of hMSCs. We applied 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrasodium bromide (MTT) assay to estimate the overall proliferative effects of the Stretch on hMSCs. We found that fibronectin coating increased adhesion to silicone chamber surface, however, it did not show significant effect on proliferation of hMSCs. A frequency of 1 Hz was more effective in stimulating hMSCs proliferation. At 1 Hz, 5% strain for 15, 30, 60 min, the significant increase of hMSCs proliferation was observed. Proliferation was enhanced at 1 Hz, 10% strain for 15, 30 min, while decreased for 60 min. At 1 Hz, 15% strain, 15 min Stretch resulted in the decrease of proliferation, and 30 min and 60 min Stretch showed an increased proliferation. Long time (12 and 24 h) strain application blocked the proliferation. These results indicate that Mechanical Stretch plays an important role in hMSCs growth and proliferation; an appropriate Mechanical Stretch regime could be a novel approach to promoting proliferation of hMSCs in vitro.
Sachi Watanabe - One of the best experts on this subject based on the ideXlab platform.
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rhoa rock cytoskeletal dynamics and focal adhesion kinase are required for Mechanical Stretch induced tenogenic differentiation of human mesenchymal stem cells
Journal of Cellular Physiology, 2012Co-Authors: Guanbin Song, Yuanhui Song, Sachi WatanabeAbstract:Human bone marrow mesenchymal stem cells (hMSCs) have the potential to differentiate into tendon/ligament-like lineages when they are subjected to Mechanical Stretching. However, the means through which Mechanical Stretch regulates the tenogenic differentiation of hMSCs remains unclear. This study examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion kinase (FAK) in Mechanical Stretch-induced tenogenic differentiation characterized by the up-regulation of tendon-related marker gene expression. Our findings showed that RhoA/ROCK and FAK regulated Mechanical Stretch-induced realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK and cytoskeletal organization were essential to Mechanical Stretch-activated FAK phosphorylation at Tyr397. We also demonstrated that this process can be blocked by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses Mechanical Stretching and drives Mechanical Stretch-induced tenogenic differentiation of hMSCs. This work provides novel insights regarding the mechanisms of tenogenesis in a Stretch-induced environment and supports the therapeutic potential of hMSCs.
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RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for Mechanical Stretch-induced tenogenic differentiation of human mesenchymal stem cells.
Journal of cellular physiology, 2012Co-Authors: Guanbin Song, Yuanhui Song, Sachi WatanabeAbstract:Human bone marrow mesenchymal stem cells (hMSCs) have the potential to differentiate into tendon/ligament-like lineages when they are subjected to Mechanical Stretching. However, the means through which Mechanical Stretch regulates the tenogenic differentiation of hMSCs remains unclear. This study examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion kinase (FAK) in Mechanical Stretch-induced tenogenic differentiation characterized by the up-regulation of tendon-related marker gene expression. Our findings showed that RhoA/ROCK and FAK regulated Mechanical Stretch-induced realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK and cytoskeletal organization were essential to Mechanical Stretch-activated FAK phosphorylation at Tyr397. We also demonstrated that this process can be blocked by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses Mechanical Stretching and drives Mechanical Stretch-induced tenogenic differentiation of hMSCs. This work provides novel insights regarding the mechanisms of tenogenesis in a Stretch-induced environment and supports the therapeutic potential of hMSCs.
Heikki Ruskoaho - One of the best experts on this subject based on the ideXlab platform.
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Mechanical Stretch induced transcriptomic profiles in cardiac myocytes
Scientific Reports, 2018Co-Authors: Jaana Rysa, Heikki Tokola, Heikki RuskoahoAbstract:Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by Mechanical Stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in Stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P < 0.05) genes in response to 1, 4, 12, 24, and 48 hours of cyclic Mechanical Stretch. We used Ingenuity Pathway Analysis to predict functional pathways and upstream regulators of differentially expressed genes in order to identify regulatory networks that may lead to Mechanical Stretch induced hypertrophic growth of cardiomyocytes. We also performed micro (miRNA) expression profiling of Stretched NRVMs, and identified that a total of 8 and 87 miRNAs were significantly (P < 0.05) altered by 1–12 and 24–48 hours of Mechanical Stretch, respectively. Finally, through integration of miRNA and mRNA data, we predicted the miRNAs that regulate mRNAs potentially leading to the hypertrophic growth induced by Mechanical Stretch. These analyses predicted nuclear factor-like 2 (Nrf2) and interferon regulatory transcription factors as well as the let-7 family of miRNAs as playing roles in the regulation of Stretch-regulated genes in cardiomyocytes.
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Mechanical Stretch induced transcriptomic profiles in cardiac myocytes.
Scientific reports, 2018Co-Authors: Jaana Rysa, Heikki Tokola, Heikki RuskoahoAbstract:Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by Mechanical Stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in Stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P
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gata 4 is a nuclear mediator of Mechanical Stretch activated hypertrophic program
Journal of Biological Chemistry, 2003Co-Authors: Sampsa Pikkarainen, Heikki Tokola, Theresa Majalahtipalviainen, Risto Kerkela, Nina Hautala, Suparna Bhalla, Frederic Charron, Mona Nemer, Olli Vuolteenaho, Heikki RuskoahoAbstract:In overloaded heart the cardiomyocytes adapt to increased Mechanical and neurohumoral stress by activation of hypertrophic program, resulting in morphological changes of individual cells and specific changes in gene expression. Accumulating evidence suggests an important role for the zinc finger transcription factor GATA-4 in hypertrophic agonist-induced cardiac hypertrophy. However, its role in Stretch-induced cardiomyocyte hypertrophy is not known. We employed an in vitro Mechanical Stretch model of cultured cardiomyocytes and used rat B-type natriuretic peptide promoter as Stretch-sensitive reporter gene. Stretch transiently increased GATA-4 DNA binding activity and transcript levels, which was followed by increases in the expression of B-type natriuretic peptide as well as atrial natriuretic peptide and skeletal α-actin genes. The Stretch inducibility mapped primarily to the proximal 520 bp of the B-type natriuretic peptide promoter. Mutational studies showed that the tandem GATA consensus sites of the proximal promoter in combination with an Nkx-2.5 binding element are critical for Stretch-activated B-type natriuretic peptide transcription. Inhibition of GATA-4 protein production by adenovirus-mediated transfer of GATA-4 antisense cDNA blocked Stretch-induced increases in B-type natriuretic peptide transcript levels and the sarcomere reorganization. The proportion of myocytes with assembled sarcomeres in control adenovirus-infected cultures increased from 14 to 59% in response to Stretch, whereas the values for GATA-4 antisense-treated cells were 6 and 13%, respectively. These results show that activation of GATA-4, in cooperation with a factor binding on Nkx-2.5 binding element, is essential for Mechanical Stretch-induced cardiomyocyte hypertrophy.
Jiedu - One of the best experts on this subject based on the ideXlab platform.
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Mechanical Stretch Simulates Proliferation of Venous Smooth Muscle Cells Through Activation of the Insulin-Like Growth Factor-1 Receptor
Arteriosclerosis Thrombosis and Vascular Biology, 2007Co-Authors: Jizhongcheng, JieduAbstract:Objective— Activation and proliferation of vascular smooth muscle cells (VSMCs) occur in the venous neointima of vein grafts. VSMCs in a grafted vein are subjected to Mechanical Stretch; our goal is to understand the essential Mechanical Stretch-regulated signals that influence VSMCs during neointimal formation in vein grafts. Methods and Results— In cultured vein VSMCs, Mechanical Stretch induces proliferation and upregulation of both IGF-1 and IGF-1R. Stretch of VSMCs sustained tyrosine phosphorylation of both IGF-1R and its substrate, IRS-1; these responses were related to Mechanical Stretch-induced activation of Src and autocrine IGF-1 production. Mechanical Stretch-activated IGF-1R is functional because there is a prolonged activation of IRS-1-associated phosphatidylinositol-3 kinase (PI3K). When we knocked out IGF-1R, the Mechanical Stretch-induced increase in VSMC proliferation was blocked. To link Mechanical Stretch-activated IGF-1R cell signaling to venous VSMC proliferation in vivo, we also stud...
