Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling

The present study examined the expression profile of buffalo fetal fibroblasts (BFF) used as a feeder layer for embryonic stem (ES) cell-like cells. The expression of important growth factors was detected in cells at different passages. Mitomycin-C inactivation increased relative expression levels of ACTIVIN-A, TGF-β1, BMP-4 and GREMLIN but not of fibroblast growth factor-2 (FGF-2). The expression level of ACTIVIN-A, transforming growth factor-β1 (TGF-β1), bone morphogenetic protein-4 (BMP-4) and FGF-2 was similar in buffalo fetal fibroblast (BFF) cultured in stem cell medium (SCM), SCM + 1000 IU mL–1 leukemia inhibitory factor (LIF), SCM + 5 ng mL–1 FGF-2 or SCM + LIF + FGF-2 for 24 h whereas GREMLIN expression was higher in FGF-2-supplemented groups. In spent medium, the concentration of ACTIVIN-A was higher in FGF-2-supplemented groups whereas that of TGF-β1 was similar in SCM and LIF + FGF-2, which was higher than when either LIF or FGF-2 was used alone. Following culture of ES cell-like cells on a feeder layer for 24 h, the TGF-β1 concentration was higher with LIF+FGF-2 than with LIF or FGF-2 alone which, in turn, was higher than that in SCM. In the LIF + FGF-2 group, the concentration of TGF-β1 was lower and that of ACTIVIN-A was higher in spent medium at 24 h than at 48 h of culture. These results suggest that BFF produce signalling molecules that may help in self-renewal of buffalo ES cell-like cells.

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Transforming growth factor-β1 (TGF-β1) induces mouse precartilaginous stem cell differentiation through TGFRII-CK1ε-β-catenin signalling

International Journal of Experimental Pathology ◽

10.1111/iep.12275 ◽

2018 ◽

Vol 99 (3) ◽

pp. 113-120 ◽

Cited By ~ 1

Author(s):

Wang Qiong ◽

Gu Xiaofeng ◽

Wang Junfang

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Growth Factor ◽

Transforming Growth Factor ◽

Stem Cell Differentiation ◽

Transforming Growth Factor Β1 ◽

Tgf Β1

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Receptor mimicking TGF-β1 binding peptide for targeting TGF-β1 signaling

Biomaterials Science ◽

10.1039/d0bm01374a ◽

2021 ◽

Author(s):

David G. Belair ◽

Jae Sung Lee ◽

Anna V. Kellner ◽

Johnny Huard ◽

William L. Murphy

Keyword(s):

Biological Activity ◽

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Soluble Form ◽

Receptor Complex ◽

Binding Peptide ◽

Binding Peptides ◽

Β Receptor ◽

Tgf Β1

Transforming growth factor-β1 (TGF-β1) binding peptides were developed via biomimicry of the TGF-β1/TGF-β receptor complex to attenuate biological activity of TGF-β1 when presented either in soluble form or conjugated to synthetic biomaterials.

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Transforming growth factor β1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21Cip1/Waf1or p27Kip1

Blood ◽

10.1182/blood.v98.13.3643 ◽

2001 ◽

Vol 98 (13) ◽

pp. 3643-3649 ◽

Cited By ~ 56

Author(s):

Tao Cheng ◽

Hongmei Shen ◽

Neil Rodrigues ◽

Sebastian Stier ◽

David T. Scadden

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Stem Cell ◽

Progenitor Cell ◽

Transforming Growth Factor ◽

Hematopoietic Cells ◽

Transforming Growth Factor Β1 ◽

Primitive Cell ◽

Hematopoietic Stem ◽

Tgf Β1

Abstract The regulation of stem cell proliferation is a poorly understood process balancing rapid, massive blood cell production in times of stress with maintenance of a multipotent stem cell pool over decades of life. Transforming growth factor β1 (TGF-β1) has pleiotropic effects on hematopoietic cells, including the inhibition of primitive cell proliferation. It was recently demonstrated that the cyclin-dependent kinase inhibitors, p21Cip1/Waf1 (p21) and p27Kip1 (p27), can inhibit the proliferation of hematopoietic stem cells and progenitor cells, respectively. The relation of TGF-β1 stimulation to p21 and p27 was examined using a fine-mapping approach to gene expression in individual cells. Abundant TGF-β1 expression and p21 expression were documented in quiescent, cytokine-resistant hematopoietic stem cells and in terminally differentiated mature blood cells, but not in proliferating progenitor cell populations. TGF-β1 receptor (TβR II) was expressed ubiquitously without apparent modulation. Cell- cycle–synchronized 32D cells exposed to TGF-β1 demonstrated a marked antiproliferative effect of TGF-β1, yet neither the level of p21 mRNA nor the protein level of either p21 or p27 was altered. To corroborate these observations in primary cells, bone marrow mononuclear cells derived from mice engineered to be deficient in p21 or p27 were assessed. Progenitor and primitive cell function was inhibited by TGF-β1 equivalently in −/− and +/+ littermate controls. These data indicate that TGF-β1 exerts its inhibition on cell cycling independent of p21 and p27 in hematopoietic cells. TGF-β1 and p21 or p27 participate in independent pathways of stem cell regulation, suggesting that targeting each may provide complementary strategies for enhancing stem or progenitor cell expansion and gene transduction.

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Ac-SDKP inhibits transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00464.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. H1357-H1364 ◽

Cited By ~ 30

Author(s):

Hongmei Peng ◽

Oscar A. Carretero ◽

Edward L. Peterson ◽

Nour-Eddine Rhaleb

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Growth Factor ◽

Transforming Growth Factor ◽

Cardiac Fibroblasts ◽

Transforming Growth Factor Β1 ◽

Collagen Production ◽

Smad7 Expression ◽

Human Cardiac Fibroblasts ◽

Tgf Β1

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits collagen production and cell proliferation in cultured rat cardiac fibroblasts, but its effect on differentiation of fibroblasts into myofibroblasts is not known. High amounts of transforming growth factor-β1 (TGF-β1) have been found in fibrotic cardiac tissue. TGF-β1 converts fibroblasts into myofibroblasts, which produce more extracellular matrix proteins than fibroblasts. We hypothesized that 1) Ac-SDKP inhibits TGF-β1-induced differentiation of fibroblasts into myofibroblasts; and 2) this effect is mediated in part by blocking phosphorylation of small-mothers-against-decapentaplegic (Smad) 2 and extracellular signal-regulated kinase (ERK) 1/2. For this study, we used human fetal cardiac fibroblasts (HCFs), which do not spontaneously become myofibroblasts when cultured at low passages. We investigated the effect of Ac-SDKP on TGF-β1-induced HCF transformation into myofibroblasts, Smad2 and ERK1/2 phosphorylation, Smad7 expression, cell proliferation, and collagen production. We also investigated TGF-β1 production by HCFs stimulated with endothelin-1 (ET-1). As expected, HCFs treated with TGF-β1 transformed into myofibroblasts as indicated by increased expression of α-smooth muscle actin and a higher proportion of the embryonic isoform of smooth muscle myosin compared with untreated cells. TGF-β1 also increased Smad2 and ERK1/2 phosphorylation but did not affect Smad7 expression. In addition, TGF-β1 stimulated HCF proliferation as indicated by an increase in mitochondrial dehydrogenase activity and collagen production (hydroxyproline assay). Ac-SDKP significantly inhibited all of the effects of TGF-β1. It also inhibited ET-1-stimulated TGF-β1 production. We concluded that Ac-SDKP markedly suppresses differentiation of human cardiac fibroblasts into myofibroblasts, probably by inhibiting the TGF-β/Smad/ERK1/2 signaling pathway, and thus mediating its anti-fibrotic effects.

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Transforming Growth Factor-β1 (TGF-β1) Induces Thrombopoietin From Bone Marrow Stromal Cells, Which Stimulates the Expression of TGF-β Receptor on Megakaryocytes and, in Turn, Renders Them Susceptible to Suppression by TGF-β Itself With High Specificity

Blood ◽

10.1182/blood.v94.6.1961 ◽

1999 ◽

Vol 94 (6) ◽

pp. 1961-1970 ◽

Cited By ~ 61

Author(s):

Sumio Sakamaki ◽

Yasuo Hirayama ◽

Takuya Matsunaga ◽

Hiroyuki Kuroda ◽

Toshiro Kusakabe ◽

...

Keyword(s):

Bone Marrow ◽

Growth Factor ◽

Transforming Growth Factor ◽

High Specificity ◽

Transforming Growth Factor Β1 ◽

Lineage Specificity ◽

Β Receptor ◽

Tgf Β1

Abstract The present study was designed to test the concept that platelets release a humoral factor that plays a regulatory role in megakaryopoiesis. The results showed that, among various hematoregulatory cytokines examined, transforming growth factor-β1 (TGF-β1) was by far the most potent enhancer of mRNA expression of bone marrow stromal thrombopoietin (TPO), a commitment of lineage specificity. The TPO, in turn, induced TGF-β receptors I and II on megakaryoblasts at the midmegakaryopoietic stage; at this stage, TGF-β1 was able to arrest the maturation of megakaryocyte colony-forming units (CFU-Meg). This effect was relatively specific when compared with its effect on burst-forming unit-erythroid (BFU-E) or colony-forming unit–granulocyte-macrophage (CFU-GM). In patients with idiopathic thrombocytopenic purpura (ITP), the levels of both TGF-β1 and stromal TPO mRNA were correlatively increased and an arrest of megakaryocyte maturation was observed. These in vivo findings are in accord with the aforementioned in vitro results. Thus, the results of the present investigation suggest that TGF-β1 is one of the pathophysiological feedback regulators of megakaryopoiesis.

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