Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-β gene expression via transcriptional and post-transcriptional mechanisms

Matsubara, Hiroaki; Moriguchi, Yasutaka; Mori, Yoshihide; Masaki, Hiroya; Shibasaki, Yasunobu; Uchiyama-Tanaka, Yoko; Fujiyama, Schoichiro; Koyama, Yoko; Nose-Fujiyama, Atsuko; Iba, Satoshi; Tateishi, Eriko; Iwasaka, Toshiji

doi:10.1007/978-1-4615-4351-0_22

Cited by 9 publications

(11 citation statements)

References 57 publications

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“…Our results do not completely rule out a T3 direct regulation of these proteins; however, they reveal an additional new mechanism for ECM protein modulation mediated by EGF in the NS. Together with ours, the recent finding that fibronectin mRNA is increased by activation of the EGFR in cardiac fibroblasts (33) and EGFR gene amplification is associated with laminin overexpression in tumor cell lines (34) suggest that EGF modulation of laminin and fibronectin might be a more general process occurring in several tissues. We completely rule out a direct action of EGF FIG.…”

Section: Egf⁄mapk-pi3k Pathways Effects On Neuritogenesissupporting

confidence: 81%

Neuritogenesis Induced by Thyroid Hormone-treated Astrocytes Is Mediated by Epidermal Growth Factor/Mitogen-activated Protein Kinase-Phosphatidylinositol 3-Kinase Pathways and Involves Modulation of Extracellular Matrix Proteins

Martinez

Gomes

2002

Journal of Biological Chemistry

110

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Thyroid hormone (T3) plays a crucial role in several steps of cerebellar ontogenesis. By using a neuron-astrocyte coculture model, we have investigated the effects of T3-treated astrocytes on cerebellar neuronal differentiation in vitro. Neurons plated onto T3-astrocytes presented a 40 -60% increase on the total neurite length and an increment in the number of neurites. Treatment of astrocytes with epidermal growth factor (EGF) yielded similar results, suggesting that this growth factor might mediate T3-induced neuritogenesis. EGF and T3 treatment increased fibronectin and laminin expression by astrocytes, suggesting that astrocyte neurite permissiveness induced by these treatments is mostly due to modulation of extracellular matrix (ECM) components. Such increase in ECM protein expression as well as astrocyte permissiveness to neurite outgrowth was reversed by the specific EGF receptor tyrosine kinase inhibitor, tyrphostin. Moreover, studies using selective inhibitors of several transductionsignaling cascades indicated that modulation of ECM proteins by EGF is mainly through a synergistic activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. In this work, we provide evidence of a novel role of EGF as an intermediary factor of T3 action on cerebellar ontogenesis. By modulating the content of ECM proteins, EGF increases neurite outgrowth. Our data reveal an important role of astrocytes as mediators of T3-induced cerebellar development and partially elucidate the role of EGF and mitogen-activated protein kinase/phosphatidylinositol 3-kinase pathways on this process.

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Section: Egf⁄mapk-pi3k Pathways Effects On Neuritogenesissupporting

confidence: 81%

Neuritogenesis Induced by Thyroid Hormone-treated Astrocytes Is Mediated by Epidermal Growth Factor/Mitogen-activated Protein Kinase-Phosphatidylinositol 3-Kinase Pathways and Involves Modulation of Extracellular Matrix Proteins

Martinez

Gomes

2002

Journal of Biological Chemistry

110

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“…ANG II has been implicated in synthesis of the extracellular matrix protein collagen via both AT 1 Rs and AT 2 Rs (90,124). ANG IIinduced EGFR-and MAPK-dependent pathways may participate in matrix formation and regulation (122,193). Indeed, ACE inhibition has been shown to limit cardiac remodeling.…”

Section: Ang II and Extracellular Matrixmentioning

confidence: 99%

Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system

Mehta

Griendling²

2007

American Journal of Physiology-Cell Physiology

1,671

1,579

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Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 292: C82-C97, 2007. First published July 26, 2006; doi:10.1152/ajpcell.00287.2006.-The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein-and non-G protein-related signaling pathways, ANG II, via AT 1 receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/ STAT, focal adhesion kinase (FAK)]. AT 1R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT 1 receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology. vascular smooth muscle; NAD(P)H oxidase; tyrosine and nontyrosine receptor kinases; endothelial dysfunction; vascular disease THE RENIN-ANGIOTENSIN SYSTEM (RAS) plays a vital role in regulating the physiological processes of the cardiovascular system. Not only does it function as an endocrine system, but it also serves local paracrine and autocrine functions in tissues and organs. The primary effector molecule of this system, angiotensin II (ANG II), has emerged as a critical hormone that affects the function of virtually all organs, including heart, kidney, vasculature, and brain, and it has both beneficial and pathological effects. Acute stimulation with ANG II regulates salt/water homeostasis and vasoconstriction, modulating blood pressure, while chronic stimulation promotes hyperplasia and hypertrophy of vascular smooth muscle cells (VSMCs) (53,216). In addition, long-term exposure to ANG II also plays a vital role in cardiac hypertrophy and remodeling, in-stent restenosis, reduced fibrinolysis, and renal fibrosis.Given its diverse range of functions and its potency in affecting cardiovascular physiology, it becomes imperative to understand the characteristics of ANG II receptors and to investigate mechanisms of ANG II-induced signal transduction. Studying the varied roles of ANG II is also of tremendous im...

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“…In addition to these classical pathways, AT 1 receptors can activate tyrosine kinases, such as Jak2, Tyk2, c-Src, and Pyk2, 38 -40 and can transactivate cell surface receptors possessing an intrinsic tyrosine kinase domain (RTKs), in particular the EGF receptor. 41 This effect is at least partly mediated by heparin-binding EGF-like growth factor (HB-EGF). 42,43 Importantly, Ang II may activate different signaling pathways in cardiac fibroblasts than in cardiomyocytes.…”

Section: Autocrine and Paracrine Factors Controlling Cardiac Fibroblastsmentioning

confidence: 99%

Gene Expression in Fibroblasts and Fibrosis

Manabe

Shindo

Nagai

2002

Circulation Research

473

365

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Abstract-Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these processes, producing growth factors and cytokines that act as autocrine and paracrine factors, as well as extracellular matrix proteins and proteinases. Recent studies have shown that the interactions between cardiac fibroblasts and cardiomyocytes are essential for the progression of cardiac remodeling. This review addresses the functional role played by cardiac fibroblasts and the molecular mechanisms that govern their activity during cardiac hypertrophy and remodeling. A particular focus is the recent progress toward our understanding of the transcriptional regulatory mechanisms involved. Key Words: transcription Ⅲ fibrosis Ⅲ myofibroblast Ⅲ cardiac remodeling R egardless of the origin, injury to the heart evokes a diverse and complex array of cellular responses involving both cardiomyocytes and nonmuscle cells that initiate and sustain a process of structural remodeling of the myocardium. 1 The importance of the structural remodeling has been addressed in randomized clinical trials. 2 For example, angiotensin-converting enzyme (ACE) inhibitors, which may delay and, in some cases, reverse cardiac remodeling, have proven to have a beneficial effect on morbidity and mortality in heart failure. Thus, remodeling is now generally accepted as a key determinant of the clinical course of heart failure. 2 Cardiac remodeling is manifested clinically as changes in the size, shape, and function of the heart. 2 Histopathologically, it is characterized by a structural rearrangement of components of the normal chamber wall that involves cardiomyocyte hypertrophy, cardiac fibroblast proliferation, fibrosis, and cell death. 3 Fibrosis, which is a disproportionate accumulation of fibrillar collagen, is an integral feature of the remodeling characteristic of the failing heart. Accumulation of type I collagen, the main fibrillar collagen found in cardiac fibrosis, stiffens the ventricles and impedes both contraction and relaxation. 4 Fibrosis can also impair the electrical coupling of cardiomyocytes by separating myocytes with extracellular matrix (ECM) proteins. 3 Furthermore, fibrosis results in reduced capillary density and an increased oxygen diffusion distance that can lead to hypoxia of myocytes. 5 Thus, fibrosis profoundly affects myocyte metabolism and performance and ultimately ventricular function. 6 In the myocardium, ECM proteins are mainly produced by fibroblasts that also produce matrix metalloproteinases Original received August 19, 2002; revision received October 30, 2002; accepted October 30, 2002. From the Departments of Cardiovascular Medicine (I.M., T.S., R.N.) and Clinical Bioinformatics (I.M., R.N.), University of Tokyo, Tokyo, Japan. Correspondence to Ichiro Manabe, MD, PhD,...

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Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-β gene expression via transcriptional and post-transcriptional mechanisms

Cited by 9 publications

References 57 publications

Neuritogenesis Induced by Thyroid Hormone-treated Astrocytes Is Mediated by Epidermal Growth Factor/Mitogen-activated Protein Kinase-Phosphatidylinositol 3-Kinase Pathways and Involves Modulation of Extracellular Matrix Proteins

Neuritogenesis Induced by Thyroid Hormone-treated Astrocytes Is Mediated by Epidermal Growth Factor/Mitogen-activated Protein Kinase-Phosphatidylinositol 3-Kinase Pathways and Involves Modulation of Extracellular Matrix Proteins

Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system

Gene Expression in Fibroblasts and Fibrosis

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