TGFβ Signaling and Cardiovascular Diseases

Pardali, Evangelia; Dijke, Peter ten

doi:10.7150/ijbs.3805

Cited by 89 publications

(92 citation statements)

References 233 publications

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“…40 TGF-β signaling operates as a rheostat that controls EC differentiation having both inhibitory and stimulating effects. 53 EC sprouting has been explained by a model in which TGF-β synergizes with VEGF and Notch to drive migration, partly through induction of ID1, required for EC migration. 54 The link between the p53 family members and TGF-β signaling in somatic cells has been previously established and it has been suggested, but never addressed, that the p53 homologs might interact with TGF-β in development.…”

Section: Discussionmentioning

confidence: 99%

p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFβ signaling

et al. 2015

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Vasculogenesis, the establishment of the vascular plexus and angiogenesis, branching of new vessels from the preexisting vasculature, involves coordinated endothelial differentiation, proliferation and migration. Disturbances in these coordinated processes may accompany diseases such as cancer. We hypothesized that the p53 family member p73, which regulates cell differentiation in several contexts, may be important in vascular development. We demonstrate that p73 deficiency perturbed vascular development in the mouse retina, decreasing vascular branching, density and stability. Furthermore, p73 deficiency could affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is necessary for EC biology and vasculogenesis and, in particular, that DNp73 regulates EC migration and tube formation capacity by regulation of expression of pro-angiogenic factors such as transforming growth factor-β and vascular endothelial growth factors. DNp73 expression is upregulated in the tumor environment, resulting in enhanced angiogenic potential of B16-F10 melanoma cells. Our results demonstrate, by the first time, that differential p73-isoform regulation is necessary for physiological vasculogenesis and angiogenesis and DNp73 overexpression becomes a positive advantage for tumor progression due to its pro-angiogenic capacity.

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Section: Discussionmentioning

confidence: 99%

p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFβ signaling

et al. 2015

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“…TGF-β belongs to a growth factor super-family which consists of a highly evolutionary conserved group of secreted cytokines (6). The TGF-β family consists of TGF-β, activins, bone morphogenetic proteins (BMPs), nodals, inhibins and antimullerian hormone (AMH).…”

Section: Introductionmentioning

confidence: 99%

The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line

Zhang

et al. 2012

Oncology Letters

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Abstract. Human choriocarcinoma is one of the most aggressive malignant tumors characterized by early hematogenous spread to lung and brain tissues, and may be a cause of death in patients. Choriocarcinoma may occur following pregnancy and during implantation; however, trophoblastic invasion in human pregnancy is tightly regulated. The transforming growth factor-beta 1 (TGF-β1) has been suggested to play a role in controlling this process. In this study, we investigated the impact of TGF-β1 on invasion, as well as its sites of action in the TGF-β1/Smad pathway using a JEG-3 choriocarcinoma cell line. Following the treatment of cells with different doses of TGF-β1, cell invasion was observed. We also detected the expression of TGF-β receptor type I (TβR I) and TGF-β receptor type II (TβR II), Smad4, matrix metalloprotease (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in JEG-3 cells. Our data demonstrated that TGF-β1 promoted the invasive capability of JEG-3 cells depending on the downregulation of TβR I, TβR II, Smad4 and the upregulation of MMP-9 and TIMP-1. These observations suggest that TGF-β1 may play a critical role in the initiation of the trophoblastic invasion process. IntroductionA successful human pregnancy requires embryonic trophocytes to invade into the womb and adhere to the endometrium; however, this kind of invasion is strictly regulated temporospatially (1). The deregulation of the invasion process may cause a series of pregnancy-related diseases, such as hydatidiform mole and invasive mole; however, excessive invasion of trophocytes is significantly associated with the formation of placental choriocarcinoma (2). In this process, one critical step of choriocarcinoma invasion and metastasis is the degradation of the extracellular matrix (ECM), in which the MMP-9/TIMP-1 ratio plays a significant role (3,4).The main treatment for choriocarcinoma is 5-fluorouracil, which has a very good therapeutic efficacy; however, it may also cause toxic reactions, side effects and drug resistance (5). Since conventional treatments including surgery and chemotherapy often fail, it is necessary to explore the metastasis mechanisms of proliferation and invasiveness, and find a new target for drug therapy.TGF-β belongs to a growth factor super-family which consists of a highly evolutionary conserved group of secreted cytokines (6). The TGF-β family consists of TGF-β, activins, bone morphogenetic proteins (BMPs), nodals, inhibins and antimullerian hormone (AMH). TGF-β1 is the prototypic family member and is secreted as an inactive latent precursor (7,8). It plays a significant role in the control of growth and development, including the regulation of cell proliferation and differentiation, the promotion of ECM formation and suppression of the immune response (9). TGF-β1 exerts its cellular effects through TβR I, TβR II and the Smad transcription factors, which have pivotal roles in intracellular signaling (7,10). Moreover, Smad4 is an essential factor in TGF-β signaling and is a frequently mutated tumor ...

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“…The cell cycle pathways in 2D are dominated with gene sets which are involved in regulating mesodermal differentiation. It has been reported that ectodermal differentiation inhibits the mesodermal differentiation mediated by TGF-β signaling pathway [9,29,30]. Therefore, it may be interpreted that the cells in 2D are still in the transitional stage between ectodermal and mesodermal differentiation where the TGF-β signaling molecules are still active.…”

Section: Discussionmentioning

confidence: 99%

Stem Cells-Based Therapeutics for Parkinson’s Disease - A Transcriptomic Analyses During Dopaminergic Neuron Differentiation under 3- and 2- Dimensional Environments using Human Embryonic Stem Cells

et al. 2017

JSRT

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Parkinson's disease (PD) is a neurodegenerative disease which is caused by many factors including progressive degeneration of dopamine (DA)-secreting neurons which reside in the midbrain substantia nigra compacta (SNc). Current available treatments comprise of intake of DA replenishing drugs or implantation of electrical impulse device. However, the short-term effect of the treatments and risks of side effects have severely limited the widespread application of these therapies for all patients with PD. Hence, human embryonic stem cells (hESCs), which are capable of both self renewal and differentiation into all cell types of human body, could potentially provide a renewable source of surrogate DA neurons for transplantation into PD patients. One of the challenges in using hESCs therapeutically is the establishment of protocols that could effectively direct their differentiation into functional DA neurons. A specific investigation on the derivation of DA neurons was carried out by using a three-dimensional (3D) environment such as encapsulation. Characterization study by microarray was performed to analyze the global expression profile in 3D-derived DA neurons after 28 days of differentiation. In comparison to the samples of DA neuronal differentiated hESCs under 2D platform for 28 days, the analysis detected the reduced expression of gene that are involved in pluripotency or mitosis but increased expression of genes that are involved in neuronal developments such as Wnt, hedgehog and mitogen-activated protein kinase (MAPK) signaling pathway. The results suggest that the 3D differentiation system may have affected the regulatory or signalling mechanisms which enhanced the rate of differentiation towards ectoderm.

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TGFβ Signaling and Cardiovascular Diseases

Cited by 89 publications

References 233 publications

p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFβ signaling

p73 is required for endothelial cell differentiation, migration and the formation of vascular networks regulating VEGF and TGFβ signaling

The impact of TGF-β1 on the mRNA expression of TβR I, TβR II, Smad4 and the invasiveness of the JEG-3 placental choriocarcinoma cell line

Stem Cells-Based Therapeutics for Parkinson’s Disease - A Transcriptomic Analyses During Dopaminergic Neuron Differentiation under 3- and 2- Dimensional Environments using Human Embryonic Stem Cells

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