scholarly journals Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β‐dependent manner in human osteosarcoma

2015 ◽  
Vol 106 (10) ◽  
pp. 1394-1401 ◽  
Author(s):  
Xuan Jiang ◽  
Jinlu Shan ◽  
Nan Dai ◽  
Zhaoyang Zhong ◽  
Yi Qing ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dependent Manner ◽  
Human Osteosarcoma

Intracisternal administration of transforming growth factor-β evokes fever through the induction of cyclooxygenase-2 in brain endothelial cells

2008 ◽  
Vol 294 (1) ◽  
pp. R266-R275 ◽  
Author(s):  
Shigenobu Matsumura ◽  
Tetsuro Shibakusa ◽  
Teppei Fujikawa ◽  
Hiroyuki Yamada ◽  
Kiyoshi Matsumura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Proinflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cyclooxygenase 2 ◽  
Dependent Manner ◽  
Cox 2 ◽  
Β Receptor

Transforming growth factor-β (TGF-β), a pleiotropic cytokine, regulates cell proliferation, differentiation, and apoptosis, and plays a key role in development and tissue homeostasis. TGF-β functions as an anti-inflammatory cytokine because it suppresses microglia and B-lymphocyte functions, as well as the production of proinflammatory cytokines. However, we previously demonstrated that the intracisternal administration of TGF-β induces fever like that produced by proinflammatory cytokines. In this study, we investigated the mechanism of TGF-β-induced fever. The intracisternal administration of TGF-β increased body temperature in a dose-dependent manner. Pretreatment with cyclooxygenase-2 (COX-2)-selective inhibitor significantly suppressed TGF-β-induced fever. COX-2 is known as one of the rate-limiting enzymes of the PGE2 synthesis pathway, suggesting that fever induced by TGF-β is COX-2 and PGE2 dependent. TGF-β increased PGE2 levels in cerebrospinal fluid and increased the expression of COX-2 in the brain. Double immunostaining of COX-2 and von Willebrand factor (vWF, an endothelial cell marker) revealed that COX-2-expressing cells were mainly endothelial cells. Although not all COX-2-immunoreactive cells express TGF-β receptor, some COX-2-immunoreactive cells express activin receptor-like kinase-1 (ALK-1, an endothelial cell-specific TGF-β receptor), suggesting that TGF-β directly or indirectly acts on endothelial cells to induce COX-2 expression. These findings suggest a novel function of TGF-β as a proinflammatory cytokine in the central nervous system.

scholarly journals NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-β (transforming growth factor-β) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-β type I receptor

2005 ◽  
Vol 386 (3) ◽  
pp. 461-470 ◽  
Author(s):  
Go KURATOMI ◽  
Akiyoshi KOMURO ◽  
Kouichiro GOTO ◽  
Masahiko SHINOZAKI ◽  
Keiji MIYAZAWA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Ubiquitin Ligases ◽  
Transforming Growth Factor Β ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Type I ◽  
Dependent Manner ◽  
E3 Ubiquitin Ligases ◽  
Neural Precursor Cell

Inhibitory Smad, Smad7, is a potent inhibitor of TGF-β (transforming growth factor-β) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-β superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-β type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-β-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-β and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-β superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-β superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs.

scholarly journals Transforming Growth Factor-β Suppressed Id-1 Expression in a smad3-Dependent Manner in LoVo Cells

2009 ◽  
Vol 293 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Hongjiang Song ◽  
Baoliang Guo ◽  
Jianguo Zhang ◽  
Chunfang Song
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dependent Manner ◽  
Lovo Cells

scholarly journals Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway

2021 ◽  
Vol 118 (33) ◽  
pp. e2111401118
Author(s):  
Yewei Liu ◽  
Adam Lehar ◽  
Renata Rydzik ◽  
Harshpreet Chandok ◽  
Yun-Sil Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Mass ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
The Body ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Mineral Density

Skeletal muscle and bone homeostasis are regulated by members of the myostatin/GDF-11/activin branch of the transforming growth factor-β superfamily, which share many regulatory components, including inhibitory extracellular binding proteins and receptors that mediate signaling. Here, we present the results of genetic studies demonstrating a critical role for the binding protein follistatin (FST) in regulating both skeletal muscle and bone. Using an allelic series corresponding to varying expression levels of endogenous Fst, we show that FST acts in an exquisitely dose-dependent manner to regulate both muscle mass and bone density. Moreover, by employing a genetic strategy to target Fst expression only in the posterior (caudal) region of the animal, we show that the effects of Fst loss are mostly restricted to the posterior region, implying that locally produced FST plays a much more important role than circulating FST with respect to regulation of muscle and bone. Finally, we show that targeting receptors for these ligands specifically in osteoblasts leads to dramatic increases in bone mass, with trabecular bone volume fraction being increased by 12- to 13-fold and bone mineral density being increased by 8- to 9-fold in humeri, femurs, and lumbar vertebrae. These findings demonstrate that bone, like muscle, has an enormous inherent capacity for growth that is normally kept in check by this signaling system and suggest that the extent to which this regulatory mechanism may be used throughout the body to regulate tissue mass may be more significant than previously appreciated.

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.

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