scholarly journals Stem cells for cardiac regeneration and possible roles of the transforming growth factor-β superfamily

2012 ◽  
Vol 3 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Nanako Kawaguchi
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Cell Biology ◽  
Transforming Growth Factor ◽  
Methyl Cellulose ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Cardiac Stem Cells ◽  
Dependent Manner ◽  
Tgf Β1

AbstractHeart failure is a leading cause of death worldwide. Studies of stem cell biology are essential for developing efficient treatments. Recently, we established and characterized c-kit-positive cardiac stem cells from the adult rat heart. Using a MethoCult culture system with a methyl-cellulose-based medium, stem-like left-atrium-derived pluripotent cells could be regulated to differentiate into skeletal/cardiac myocytes or adipocytes with almost 100% purity. Microarray and pathway analyses of these cells showed that transforming growth factor-β1 (TGF-β1) and noggin were significantly involved in the differentiation switch. Furthermore, TGF-β1 may act as a regulator for this switch because it simultaneously inhibits adipogenesis and activates myogenesis in a dose-dependent manner. However, the effect of TGF-β varies with developmental stage, dosage, and timing of treatment. In the present review, the findings of recent studies, in particular the use of c-kit-positive cardiac stem cells, are discussed. The effects of the TGF-β superfamily on differentiation, especially on adipogenesis and/or myogenesis, have important implications for future regenerative medicine.

Transforming growth factor-β1 downregulation of Smad1 gene expression in rat hepatic stellate cells

2003 ◽  
Vol 285 (3) ◽  
pp. G539-G546 ◽  
Author(s):  
Hong Shen ◽  
Guojiang Huang ◽  
Mohammed Hadi ◽  
Patrick Choy ◽  
Manna Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Dependent Manner ◽  
Tgf Β1

Smads are intracellular signaling molecules of the transforming growth factor-β (TGF-β) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGF-β significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-β1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF-β1 significantly inhibits the expression of the Smad1 gene.

scholarly journals Studies on the Biological Effects of Ozone: 10. Release of Factors from Ozonated Human Platelets

1999 ◽  
Vol 8 (4-5) ◽  
pp. 205-209 ◽  
Author(s):  
G. Valacchi ◽  
Velio Bocci
Keyword(s):  
Platelet Aggregation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Biological Effects ◽  
Transforming Growth Factor Β1 ◽  
Human Platelets ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Tgf Β1

In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor β1 (TGF-β1) and interleukin-8(IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limbischemia treated with O3autohaemoteraphy (O3-AHT).

scholarly journals Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release

1997 ◽  
Vol 322 (3) ◽  
pp. 809-814 ◽  
Author(s):  
Kazushi IMAI ◽  
Ari HIRAMATSU ◽  
Daikichi FUKUSHIMA ◽  
Michael D. PIERSCHBACHER ◽  
Yasunori OKADA
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinases ◽  
Transforming Growth Factor ◽  
Core Protein ◽  
Chondroitin Sulphate ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Extracellular Milieu ◽  
Tissue Reactions ◽  
Tgf Β1

Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached to a single dermatan/chondroitin sulphate glycosaminoglycan chain. It may play a role in regulation of collagen fibrillogenesis and function as a reservoir of transforming growth factor β(TGF-β) in the extracellular milieu. We have examined the susceptibility of DCN to five different matrix metalloproteinases (MMPs): MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7 (matrilysin) and MMP-9 (gelatinase B). MMP-2 and MMP-3 digest DCN into seven major fragments in a similar pattern. The N-terminal sequence of the two fragments generated by MMP-2 and MMP-3 is Leu211-Lys-Gly-Leu-Asn, but that of the others is Asp1-Glu-Ala-Ser-Gly. MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn. Activities of MMP-1 and MMP-9 against DCN are negligible. The values of Km for the MMPs capable of degrading DCN are very similar (10–12 μM), but the kcat/Km value for MMP-7 (30.5 μM-1·h-1) is 4.5-fold higher than those for MMP-2 and MMP-3. Incubation of a DCN–TGF-β1 complex with MMP-2, -3 or -7 results in release of TGF-β1 from the complex. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-β1 released from DCN in the connective tissues.

scholarly journals TGF-β1 869T/C Polymorphism and Ischemic Stroke: Sex Difference in Chinese

2010 ◽  
Vol 37 (6) ◽  
pp. 803-807 ◽  
Author(s):  
Hong-miao Tao ◽  
Guo-zhong Chen ◽  
Xiao-dong Lu ◽  
Gan-ping Chen ◽  
Bei Shao
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Chinese Patients ◽  
Cerebrovascular Complications ◽  
Specific Association ◽  
Female Specific ◽  
Tgf Β1

AbstractBackground:Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cerebrovascular complications. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine with a central role in inflammation. To investigate whether polymorphisms of the TGF-β1 gene can modify the risk of ischemic stroke (IS) in Chinese population, we conduct this hospital-based, case-control study.Methods:Transforming growth factor-β1 genotype was determined in 450 Chinese patients (306 male and 144 female) with IS and 450 control subjects (326 male and 124 female).Results:Subjects carrying 869TT were susceptible to IS (odds ratio [OR] =1.58; P=0.003). Further analysis of IS data partitioned by gender revealed the female-specific association with 869T/C (OR=2.64; P=0.001).Conclusions:Findings suggest that the TT genotype of 869T/C might be a risk factor of IS in Chinese, especially in females.

scholarly journals NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells

2019 ◽  
Author(s):  
P García-Gómez ◽  
M Dadras ◽  
C Bellomo ◽  
A Mezheyeuski ◽  
K Tzavlaki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Ros Production ◽  
Self Renewal ◽  
Glioblastoma Stem Cells ◽  
Nadph Oxidase 4

ABSTRACTGlioblastoma (GBM) is the most aggressive and common glioma subtype with a median survival of 15 months after diagnosis. Current treatments have limited therapeutic efficacy, thus more effective approaches are needed. The glioblastoma tumoral mass is characterized by a small cellular subpopulation, the Glioblastoma stem cells (GSCs), which has been held accountant for initiation, invasion, proliferation, relapse and resistance to chemo- and radiotherapy. Targeted therapies against GSCs are crucial, and so is the understanding of the molecular mechanisms that govern the GSCs. Transforming growth factor β (TGFβ), platelet growth factor (PDGF) signalling and Reactive Oxygen Species (ROS) production govern and regulate cancer-stem cell biology. In this work, we focus on the role of the NADPH oxidase 4 (NOX4) downstream of TGFβ signalling in the GSCs. NOX4 utilises NADPH to generate ROS; TGFβ induces NOX4 expression, thus increasing ROS production. Interestingly, NOX4 itself regulates GSC self-renewal and modulates Since TGFβ regulates PDGFB in GSC, we analysed how PDGFB modulates NOX4 expression and increases ROS production. Both TGFβ and PDGF signalling regulate GSC proliferation in a NOX4/ROS-dependent manner. The transcription factor NRF2, involved in the transcriptional regulation of antioxidant and metabolic responses, is regulated by both TGFβ and NOX4. This results in an antioxidant response, which positively contributes to GSC self-renewal and proliferation. In conclusion, this work functionally establishes NOX4 as a key mediator of GSC biology.

scholarly journals Human Papillomavirus Type 5 E6 Oncoprotein Represses the Transforming Growth Factor β Signaling Pathway by Binding to SMAD3

2006 ◽  
Vol 80 (24) ◽  
pp. 12420-12424 ◽  
Author(s):  
Jose-Andres Mendoza ◽  
Yves Jacob ◽  
Patricia Cassonnet ◽  
Michel Favre
Keyword(s):  
Human Papillomavirus ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Cellular Transformation ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
E6 Oncoprotein ◽  
E6 Protein ◽  
Tgf Β1

ABSTRACT Mechanisms of cellular transformation associated with human papillomavirus type 5 (HPV5), which is responsible for skin carcinomas in epidermodysplasia verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid screening and molecular and cellular biology experiments, we found that HPV5 oncoprotein E6 interacts with SMAD3, a key component in the transforming growth factor β1 (TGF-β1) signaling pathway. HPV5 E6 inhibits SMAD3 transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF-β1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.

scholarly journals A Role for Endogenous Transforming Growth Factor β1 in Langerhans Cell Biology:  The Skin of   Transforming Growth Factor β1 Null Mice Is Devoid of  Epidermal Langerhans Cells

1996 ◽  
Vol 184 (6) ◽  
pp. 2417-2422 ◽  
Author(s):  
Teresa A. Borkowski ◽  
John J. Letterio ◽  
Andrew G. Farr ◽  
Mark C. Udey
Keyword(s):  
Growth Factor ◽  
Epidermal Cell ◽  
Cell Biology ◽  
Langerhans Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cell Suspensions ◽  
Wasting Syndrome ◽  
Tgf Β1 ◽  
Epidermal Langerhans Cells

Transforming growth factor β1 (TGF-β1) regulates leukocytes and epithelial cells. To determine whether the pleiotropic effects of TGF-β1, a cytokine that is produced by both keratinocytes and Langerhans cells (LC), extend to epidermal leukocytes, we characterized LC (the epidermal contingent of the dendritic cell [DC] lineage) and dendritic epidermal T cells (DETC) in TGF-β1 null (TGF-β1 −/−) mice. I-A+ LC were not detected in epidermal cell suspensions or epidermal sheets prepared from TGF-β1 −/− mice, and epidermal cell suspensions were devoid of allostimulatory activity. In contrast, TCR-γδ+ DETC were normal in number and appearance in TGF-β1 −/− mice and, importantly, DETC represented the only leukocytes in the epidermis. Immunolocalization studies revealed CD11c+ DC in lymph nodes from TGF-β1 −/− mice, although gp40+ DC were absent. Treatment of TGF-β1 −/− mice with rapamycin abrogated the characteristic inflammatory wasting syndrome and prolonged survival indefinitely, but did not result in population of the epidermis with LC. Thus, the LC abnormality in TGF-β1 −/− mice is not a consequence of inflammation in skin or other organs, and LC development is not simply delayed in these animals. We conclude that endogenous TGF-β1 is essential for normal murine LC development or epidermal localization.

scholarly journals Corticosteroid inhibits differentiation of palmar fibromatosis-derived stem cells (FSCs) through downregulation of transforming growth factor-β1 (TGF-β1)

PLoS ONE ◽  
2018 ◽  
Vol 13 (6) ◽  
pp. e0198326
Author(s):  
Jung-Pan Wang ◽  
Hsiang-Hsuan Michael Yu ◽  
En-Rung Chiang ◽  
Jir-You Wang ◽  
Po- Hsin Chou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Palmar Fibromatosis ◽  
Tgf Β1

scholarly journals Transforming Growth Factor- β1 Signaling in Vascular Endothelial Cells Inhibits Hematopoietic Stem Cell Regeneration

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1493-1493
Author(s):  
Derek Zachman ◽  
Devorah C Goldman ◽  
Chandan Guha ◽  
Beth Wilmot ◽  
William H. Fleming
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Conflicts Of Interest ◽  
Umbilical Vein ◽  
Transforming Growth Factor Β1 ◽  
Dependent Manner ◽  
Hematopoietic Stem ◽  
Tgf Β1

Abstract Endothelial cells (EC) are known to be essential for hematopoietic regeneration; however, little is known about the pathways that regulate this activity. By modeling endothelial-dependent HSC interactions in vitro, we found that human umbilical vein endothelial cells (HUVEC) had a markedly reduced capacity to regenerate functional CD150+LSK cells (HSC) compared to other sources of arterial and venous EC. Transcriptional profiling revealed the overexpression of transforming growth factor- β1 (TGF-β1) in HUVEC and indicated that TGF-β1 driven transcriptional programs are highly active in these cells, a finding consistent with autocrine TGF-β1 signaling. Functional studies demonstrated that HSC regeneration by EC was potently inhibited by TGF-β1 and augmented by the ALK5 inhibitor SB431542, in a dose-dependent manner. Importantly, exposure of EC alone to TGF- β1 was sufficient to attenuate subsequent HSC self-renewal. Transcriptome analysis also identified hepatocyte growth factor (HGF) as a candidate EC-derived factor with the potential to enhance hematopoietic regeneration. HGF treatment of HUVEC activated endothelial Akt signaling and led to a >10-fold increase in HSC regeneration that could be blocked by the c-Met inhibitor PF04217903. HGF treatment also dramatically increased long-term multi-lineage hematopoiesis from HUVEC regenerated HSC. Our findings reveal a novel suppressive role for TGF-β1 in the vascular niche and demonstrate that EC-derived growth factors such as HGF have the potential to attenuate this suppression and significantly enhance HSC regeneration. Disclosures No relevant conflicts of interest to declare.

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