共查询到20条相似文献,搜索用时 29 毫秒
1.
Gudrun Valdimarsdottir Marie-José Goumans Fumiko Itoh Susumu Itoh Carl-Henrik Heldin Peter ten Dijke 《BMC cell biology》2006,7(1):16-11
Background
In endothelial cells (EC), transforming growth factor-β (TGF-β) can bind to and transduce signals through ALK1 and ALK5. The TGF-β/ALK5 and TGF-β/ALK1 pathways have opposite effects on EC behaviour. Besides differential receptor binding, the duration of TGF-β signaling is an important specificity determinant for signaling responses. TGF-β/ALK1-induced Smad1/5 phosphorylation in ECs occurs transiently. 相似文献2.
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Degradation of SnoN is thought to play an important role in the transactivation of TGF-beta responsive genes. We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC. These results suggest that APC(CDH1) and SnoN play central roles in regulating growth through the TGF-beta signaling system. 相似文献
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Riera KM Rothfusz NE Wilusz RE Weinberg JB Guilak F McNulty AL 《Arthritis research & therapy》2011,13(6):R187
Introduction
Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair. 相似文献6.
Activation of extracellular signal-regulated kinase by TGF-β1 via TβRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells 总被引:1,自引:0,他引:1
Huo YY Hu YC He XR Wang Y Song BQ Zhou PK Zhu MX Li G Wu DC 《Cell biology and toxicology》2007,23(2):113-128
Transforming growth factor-β1 (TGF-β1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The
mechanism of this activation is not well elucidated. Here, we explore the role of TGF-β/Smads signaling compounds in TGF-β1-mediated
activation of extracellular signal-regulated kinase (ERK) MAPK in human papillomavirus (HPV)-18 immortalized human bronchial
epithelial cell line BEP2D and the role of TGF-β1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D.
The cell models of siRNA-mediated silencing of TGF-β receptor type II (TβRII), Smad2, Smad3, Smad4, and Smad7 were employed
in this study. Our results demonstrate that TGF-β1 activates ERK in a time-dependent manner with a maximum effect at 60 min;
overexpression of Smad7 increased this TGF-β1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of TβRII,
Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-β1-mediated
ERK phosphorylation in Smad4 knockdown cells but not in TβRII knockdown cells. In BEP2D cells, TGF-β1 treatment effectively
inhibited cells’ proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly
enhanced the TGF-β1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that TβRII
and Smad7 play the critical roles in TGF-β1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through
up-regulating Smad7 expression; and TGF-β1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and
apoptosis regulation. 相似文献
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Transforming Growth Factor-β (TGF-β) plays an essential role in differentiation of dental pulp cells into odontoblasts during reparative dentine formation. However, the mechanism by which TGF-β stimulates dental repair remains rather obscure. Human dental pulp cells were used as an in vitro model in the present work. We showed that TGF-β signaled through mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38, along with Smad pathway. Distinct pathways exerted different time response. SB203580, a specific p38 MAPK inhibitor, reduced phosphorylation of Smad3, while it slightly enhanced phosphorylation of Smad2. Increased phosphorylation of ERK1/2 and p38 confirmed that SB203580 did not block activation of TGF-β receptors. In addition, the inhibition of ERK1/2 activity with MEK1/2 inhibitor U0126 increased TGF-β mediated phosphorylation of Smad3. Our results suggest that p38 affects the phosphorylation of Smad2 and Smad3 differentially during TGF-β signaling in human dental pulp cells and ERK1/2 might be involved in the process. 相似文献
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Zhao XY Zhao LY Zheng QS Su JL Guan H Shang FJ Niu XL He YP Lu XL 《Molecular and cellular biochemistry》2008,310(1-2):159-166
Mast cell-derived chymase is implicated in myocardial fibrosis (MF), but the underlying mechanism of intracellular signaling
remains unclear. Transforming growth factor-β1 (TGF-β1) is identified as the most important profibrotic cytokine, and Smad
proteins are essential, but not exclusive downstream components of TGF-β1 signaling. Moreover, novel evidence indicates that
there is a cross talk between Smad and mitogen-activated protein kinase (MAPK) signaling cascade. We investigated whether
chymase activated TGF-β1/Smad pathway and its potential role in MF by evaluating cardiac fibroblasts (CFs) proliferation and
collagen synthesis in neonatal rats. MTT assay and 3H-Proline incorporation revealed that chymase induced CFs proliferation and collagen synthesis in a dose-dependent manner.
RT-PCR and Western blot assay demonstrated that chymase not only increased TGF-β1 expression but also upregulated phosphorylated-Smad2/3
protein. Furthermore, pretreatment with TGF-β1 neutralizing antibody suppressed chymase-induced cell growth, collagen production,
and Smad activation. In contrast, the blockade of angiotensin II receptor had no effects on chymase-induced production of
TGF-β1 and profibrotic action. Additionally, the inhibition of MAPK signaling had no effect on Smad activation elicited by
chymase. These results suggest that chymase can promote CFs proliferation and collagen synthesis via TGF-β1/Smad pathway rather
than angiotensin II, which is implicated in the process of MF. 相似文献
10.
Qingwei Zhu Yong Hwan Kim Douglas Wang S. Paul Oh Kunxin Luo 《The Journal of cell biology》2013,202(6):937-950
In endothelial cells, two type I receptors of the transforming growth factor β (TGF-β) family, ALK1 and ALK5, coordinate to regulate embryonic angiogenesis in response to BMP9/10 and TGF-β. Whereas TGF-β binds to and activates ALK5, leading to Smad2/3 phosphorylation and inhibition of endothelial cell proliferation and migration, BMP9/10 and TGF-β also bind to ALK1, resulting in the activation of Smad1/5. SnoN is a negative regulator of ALK5 signaling through the binding and repression of Smad2/3. Here we uncover a positive role of SnoN in enhancing Smad1/5 activation in endothelial cells to promote angiogenesis. Upon ligand binding, SnoN directly bound to ALK1 on the plasma membrane and facilitated the interaction between ALK1 and Smad1/5, enhancing Smad1/5 phosphorylation. Disruption of this SnoN–Smad interaction impaired Smad1/5 activation and up-regulated Smad2/3 activity. This resulted in defective angiogenesis and arteriovenous malformations, leading to embryonic lethality at E12.5. Thus, SnoN is essential for TGF-β/BMP9-dependent biological processes by its ability to both positively and negatively modulate the activities of Smad-dependent pathways. 相似文献
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Background
Functional antagonism between transforming growth factor beta (TGF-β) and hyaluronidase has been demonstrated. For example, testicular hyaluronidase PH-20 counteracts TGF-β1-mediated growth inhibition of epithelial cells. PH-20 sensitizes various cancer cells to tumor necrosis factor (TNF) cytotoxicity by upregulating proapoptotic p53 and WW domain-containing oxidoreductase (WOX1). TGF-β1 blocks PH-20-increased TNF cytotoxicity. In the present study, the functional antagonism between TGF-β1 and lysosomal hyaluronidases Hyal-1 and Hyal-2 was examined. 相似文献14.
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Candela R Gonzalez María E Matzkin Mónica B Frungieri Claudio Terradas Roberto Ponzio Elisa Puigdomenech Oscar Levalle Ricardo S Calandra Silvia I Gonzalez-Calvar 《Reproductive biology and endocrinology : RB&E》2010,8(1):148
Background
In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertility. 相似文献16.
Background
The transforming growth factor-β (TGF-β) family constitutes of dimeric proteins that regulate the growth, differentiation and metabolism of many cell types, including that of skeletal muscle in mammals. The potential role of TGF-βs in fish muscle growth is not known. 相似文献17.
Atrophin-1-interacting protein 4 (AIP4) is the human homolog of the mouse Itch protein (hItch), an E3 ligase for Notch and JunB. Human enhancer of filamentation 1 (HEF1) has been implicated in signaling pathways such as those mediated by integrin, T cell receptor, and B cell receptor and functions as a multidomain docking protein. Recent studies suggest that HEF1 is also involved in the transforming growth factor-beta (TGF-beta) signaling pathways, by interacting with Smad3, a key signal transducer downstream of the TGF-beta type I receptor. The interaction of Smad3 with HEF1 induces HEF1 proteasomal degradation, which was further enhanced by TGF-beta stimulation. The detailed molecular mechanisms of HEF1 degradation regulated by Smad3 were poorly understood. Here we report our studies that demonstrate the function of AIP4 as an ubiquitin E3 ligase for HEF1. AIP4 forms a complex with both Smad3 and HEF1 through its WW domains in a TGF-beta-independent manner and regulates HEF1 ubiquitination and degradation, which can be enhanced by TGF-beta stimulation. These findings reveal a new mechanism for Smad3-regulated proteasomal degradation events and also broaden the network of cross-talk between the TGF-beta signaling pathway and those involving HEF1 and AIP4. 相似文献
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Xu GP Li QQ Cao XX Chen Q Zhao ZH Diao ZQ Xu ZD 《Cellular & molecular biology letters》2007,12(3):457-472
The aim of this study was to investigate whether transforming growth factor-β1 (TGF-β1) could induce alveolar epithelial-mesenchymal
transition (EMT) in vitro, and whether Smad7 gene transfer could block this transition. We also aimed to elucidate the possible mechanisms of these
processes. The Smad7 gene was transfected to the rat type II alveolar epithelial cell line (RLE-6TN). Expression of the EMT-associated
markers was assayed by Western Blot and Real-time PCR. Morphological alterations were examined via phase-contrast microscope
and fluorescence microscope, while ultrastructural changes were examined via electron microscope. TGF-β1 treatment induced
a fibrotic phenotype of RLE-6TN with increased expression of fibronectin (FN), α-smooth muscle actin (α-SMA) and vimentin,
and decreased expression of E-cadherin (E-cad) and cytokeratin19 (CK19). After transfecting the RLE-6TN with the Smad7 gene,
the expression of the mesenchymal markers was downregulated while that of the epithelial markers was upregulated. TGF-β1 treatment
for 48 h resulted in the separation of RLE-6TN from one another and a change into elongated, myofibroblast-like cells. After
the RLE-6TN had been transfected with the Smad7 gene, TGF-β1 treatment had no effect on the morphology of the RLE-6TN. TGF-β1
treatment for 48 h resulted in an abundant expression of α-SMA in the RLE-6TN. If the RLE-6TN were transfected with the Smad7
gene, TGF-β1 treatment for 48 h could only induce a low level of α-SMA expression. Furthermore, TGF-β1 treatment for 12 h
resulted in the degeneration and swelling of the osmiophilic multilamellar bodies, which were the markers of type II alveolar
epithelial cells. TGF-β1 can induce alveolar epithelialmesenchymal transition in vitro, which is dependent on the Smads signaling pathway to a certain extent. Overexpression of the Smad7 gene can partially block
this process 相似文献
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Lance E Wyatt Chi Y Chung Brian Carlsen Akiko Iida-Klein George H Rudkin Kenji Ishida Dean T Yamaguchi Timothy A Miller 《BMC cell biology》2001,2(1):14-6