共查询到20条相似文献,搜索用时 31 毫秒
1.
Dominique Langlois Mohammad Hneino Lamia Bouazza Ara Parlakian Takako Sasaki Giampiero Bricca Jacques Yuan Li 《Transgenic research》2010,19(6):1069-1082
To understand the role of TGF-β signaling in cardiovascular development, we generated mice with conditional deletion of the
TGF-β type II receptor (TβRII) gene (Tgfbr2) in cells expressing the smooth muscle cell-specific protein SM22α. The SM22α promoter was active in tissues involved in cardiovascular development: vascular smooth muscle cells (VSMCs), epicardium and
myocardium. All SM22-Cre+/−/Tgfbr2
flox/flox embryos died during the last third of gestation. About half the mutant embryos exhibited heart defects (ventricular myocardium
hypoplasia and septal defects). All mutant embryos displayed profound vascular abnormalities in the descending thoracic aorta
(irregular outline and thickness, occasional aneurysms and elastic fiber disarray). Restriction of these defects to the descending
thoracic aorta occurred despite similar levels of Tgfbr2 invalidation in the other portions of the aorta, the ductus arteriosus and the pulmonary trunk. Immunocytochemistry identified
impairment of VSMC differentiation in the coronary vessels and the descending thoracic aorta as crucial for the defects. Ventricular
myocardial hypoplasia, when present, was associated to impaired α-SMA differentiation of the epicardium-derived coronary VSMCs.
Tgfbr2 deletion in the VSMCs of the descending thoracic aorta diminished the number of α-SMA-positive VSMC progenitors in the media
at E11.5 and drastically decreased tropoelastin (from E11.5) and fibulin-5 (from E.12.5) synthesis and/or deposition. Defective
elastogenesis observed in all mutant embryos and the resulting dilatation and probable rupture of the descending thoracic
aorta might explain the late embryonic lethality. To conclude, during mouse development, TGF-β plays an irreplaceable role
on the differentiation of the VSMCs in the coronary vessels and the descending thoracic aorta. 相似文献
2.
The sodium/iodide symporter (SLC5A5, also known as NIS) is a transmembrane glycoprotein. Physiologically, iodide transportation in the mammary gland occurs during late pregnancy
and lactation. To identify factors that may regulate this process at different iodine levels, we have studied the expression
of NIS gene and protein in cultured mammary gland explants from lactating mice by real-time quantitative PCR and In-Cell Western
methods. Mammary gland cells were grown in media with different levels of iodine for 24 h. The iodine treatment groups consist
of low iodine group I (LI-I, 0 μg/l), low iodine group II (LI-II, 5 μg/l), control group (C, 50 μg/l), high iodine group I
(HI-I, 3,000 μg/l), and high iodine group II (HI-II, 10,000 μg/l). The cells were then incubated with or without insulin-like
growth factor I (IGF-I) or transforming growth factor β1 (TGF-β1) for another 24 h. We found that iodine inhibited NIS mRNA and protein expression in a dose-dependent manner. IGF-I and TGF-β1 further decreased NIS mRNA and protein expression that iodine inhibited at different iodine levels. In summary, we have shown that iodine downregulated
NIS expression in cultured mammary gland explants from the lactating mouse. IGF-I and TGF-β1 inhibited NIS mRNA and protein expression in the mammary gland under different iodine levels. 相似文献
3.
Peng Qi Yue-ming Chen Hao Wang Meng Fang Qiang Ji Yun-peng Zhao Xiao-juan Sun Yan Liu Chun-fang Gao 《Cancer immunology, immunotherapy : CII》2009,58(9):1433-1440
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The risk for developing HCC increases
with severity of inflammation and fibrosis. Transforming growth factor-β1 (TGF-β1) is most frequently upregulated in tumor
cells. The most studied −509C>T polymorphism of TGF-β1 gene has been associated with colorectal, gynecologic, and lung cancers.
To assess whether this polymorphism in TGF-β1 gene is associated with susceptibility to and/or clinicopathologic characteristics
of HBV-related HCC, a total of 575 patients with chronic HBV infection and 299 healthy volunteers with no evidence of recent
or remote HBV infection were prospectively enrolled. The patients were divided into two groups: those without (n = 196) and those with HCC (n = 379). These 379 HCC patients with chronic HBV infection were designated as cases, the remaining 196 patients without HCC
and 299 healthy volunteers served as disease and healthy controls, respectively. −509C>T polymorphism in the TGF-β1 gene promoter
was studied using restriction fragment-length polymorphism. In addition, tumor tissues of liver (n = 60) were obtained from the studied HCC patients for measurement of TGF-β1 mRNA expression levels. We also assessed the
plasma TGF-β1 levels of HBV patients without (n = 94) or with HCC (n = 136) and healthy subjects (n = 120). In our study group, the risk of HCC in Chinese patients with HBV infection was significantly lower with the TT genotypes
than in those with the CC genotypes at position −509 of TGF-β1 gene (P = 0.01). In addition, in the case group, patients with the CC genotype had a statistically significant higher median plasma
TGF-β1 or liver tumor tissue TGF-β1 mRNA level compared with the individuals with the TT genotype. However, in a subsequent
analysis of the association between this polymorphism and clinicopathological characteristics including tumor number, size,
grade, stage, and invasiveness, there was no significant difference in both the distribution of genotype or allelic frequency
within HCC patients, indicating that −509C>T exchange in TGF-β1 gene may play an important role in the occurrence, not the
progression of HBV-related HCC through influencing plasma concentrations of TGF-β1 or TGF-β1 mRNA expression of liver tumor
tissue. 相似文献
4.
Katri Lindfors Keijo M Viiri Marjo Niittynen Taisto YK Heinonen Markku M?ki Heikki Kainulainen 《BMC genomics》2003,4(1):53
Background
We have previously set up an in vitro mesenchymal-epithelial cell co-culture model which mimics the intestinal crypt villus axis biology in terms of epithelial cell differentiation. In this model the fibroblast-induced epithelial cell differentiation from secretory crypt cells to absorptive enterocytes is mediated via transforming growth factor-β (TGF-β), the major inhibitory regulator of epithelial cell proliferation known to induce differentiation in intestinal epithelial cells. The aim of this study was to identify novel genes whose products would play a role in this TGF-β-induced differentiation. 相似文献5.
Jennifer J Hill Tammy-Lynn Tremblay Christiane Cantin Maureen O'Connor-McCourt John F Kelly Anne EG Lenferink 《Proteome science》2009,7(1):2-17
Background
TGF-β acts as an antiproliferative factor in normal epithelial cells and at early stages of oncogenesis. However, later in tumor development TGF-β can become tumor promoting through mechanisms including the induction of epithelial-to-mesenchymal transition (EMT), a process that is thought to contribute to tumor progression, invasion and metastasis. To identify EMT-related breast cancer therapeutic targets and biomarkers, we have used two proteomic approaches to find proteins that change in abundance upon the induction of EMT by TGF-β in two mouse mammary epithelial cell lines, NMuMG and BRI-JM01. 相似文献6.
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7.
James M Wells Farzad Esni Gregory P Boivin Bruce J Aronow William Stuart Chelsea Combs Angela Sklenka Steven D Leach Andrew M Lowy 《BMC developmental biology》2007,7(1):4
Background
β-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of β-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that β-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of β-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of β-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of β-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed β-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis. 相似文献8.
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9.
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Background
Little is known about the affect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a β-actin promoter, we examined the affect of simulated-microgravity on GFP expression in the heart, notochord, eye, somites, and rohon beard neurons. We exposed transgenic zebrafish to simulated-microgravity for different durations at a variety of developmental times in an attempt to determine periods of susceptibility for the different developing organ systems. 相似文献11.
The transforming growth factor-beta (TGF-β) 1 is a mediator of extracellular matrix (ECM) gene expression in mesangial cells
and the development of diabetic glomerulopathy. Here, we investigate the effects of TGF-β1 on laminin γ1 and fibronectin polypeptide
expression and cell survival in mouse mesangial cells (MES-13). TGF-β1 (10 ng/ml) stimulates laminin-γ1 and fibronectin expression
~two-fold in a time-dependent manner (0–48 h). TGF-β1 treatment also retards laminin-γ1 mobility on SDS-gels, and tunicamycin,
an inhibitor of the N-linked glycosylation, blocks the mobility shift. TGF-β1 increases the binding of laminin γ1 to WGA-agarose
and the binding is abolished by tunicamycin suggesting that laminin γ1 is modified by N-linked glycosylation. TGF-β1 also
elevates fibronectin glycosylation but its mobility is not altered. The degradation of laminin γ1 and fibronectin proteins
is reduced by their glycosylation. In addition, TGF-β1 enhances mesangial cell viability and metabolic activities initially
(0–24 h); however, eventually leads to cell death (24–48 h). TGF-β1 elevates pro-apoptotic caspase-3 activity and decrease
cell cycle progression factor cyclin D1 expression, which parallels cell death. These results indicate that TGF-β1 plays an
important role in ECM expression, protein glycosylation and demise of mesangial cells in the diabetic glomerular mesangium.
(Mol Cell Biochem 278: 165–175, 2005) 相似文献
12.
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
Background
Bone morphogenetic proteins (BMPs) and transforming growth factor-βs (TGF-βs) are important regulators of bone repair and regeneration. BMP-2 and TGF-β1 have been shown to inhibit gap junctional intercellular communication (GJIC) in MC3T3-E1 cells. Connexin 43 (Cx43) has been shown to mediate GJIC in osteoblasts and it is the predominant gap junctional protein expressed in these murine osteoblast-like cells. We examined the expression, phosphorylation, and subcellular localization of Cx43 after treatment with BMP-2 or TGF-β1 to investigate a possible mechanism for the inhibition of GJIC. 相似文献13.
Emma C Derrett-Smith Audrey Dooley Korsa Khan Xu Shi-wen David Abraham Christopher P Denton 《Arthritis research & therapy》2010,12(2):R69
Introduction
Vasculopathy, including altered vasoreactivity and abnormal large vessel biomechanics, is a hallmark of systemic sclerosis (SSc). However, the pathogenic link with other aspects of the disease is less clear. To assess the potential role of transforming growth factor beta (TGF-β) overactivity in driving these cardiovascular abnormalities, we studied a novel transgenic mouse model characterized by ligand-dependent activation of TGF-β signaling in fibroblasts. 相似文献14.
15.
TGF-β superfamily members signal through a heteromeric receptor complex to regulate craniofacial development. TGF-β type II receptor appears to bind only TGF-β, whereas TGF-β type I receptor (ALK5) also binds to ligands in addition to TGF-β. Our previous work has shown that conditional inactivation of Tgfbr2 in the neural crest cells of mice leads to severe craniofacial bone defects. In this study, we examine and compare the defects of TGF-β type II receptor (Wnt1-Cre;Tgfbr2fl/fl) and TGF-β type I receptor/Alk5 (Wnt1-Cre;Alk5fl/fl) conditional knockout mice. Loss of Alk5 in the neural crest tissue resulted in phenotypes not seen in the Tgfbr2 mutant, including delayed tooth initiation and development, defects in early mandible patterning and altered expression of key patterning genes including Msx1, Bmp4, Bmp2, Pax9, Alx4, Lhx6/7 and Gsc. Alk5 controls the survival of CNC cells by regulating expression of Gsc and other genes in the proximal aboral region of the developing mandible. We conclude that ALK5 regulates tooth initiation and early mandible patterning through a pathway independent of Tgfbr2. There is an intrinsic requirement for Alk5 signal in regulating the fate of CNC cells during tooth and mandible development. 相似文献
16.
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17.
Oka K Oka S Hosokawa R Bringas P Brockhoff HC Nonaka K Chai Y 《Developmental biology》2008,321(2):303-309
Transforming growth factor-β (TGF-β) signaling is crucial for mandible development. During its development, the majority of the mandible is formed through intramembranous ossification whereas the proximal region of the mandible undergoes endochondral ossification. Our previous work has shown that TGF-β signaling is required for the proliferation of cranial neural crest (CNC)-derived ectomesenchyme in the mandibular primordium where intramembranous ossification takes place. Here we show that conditional inactivation of Tgfbr2 in CNC cells results in accelerated osteoprogenitor differentiation and perturbed chondrogenesis in the proximal region of the mandible. Specifically, the appearance of chondrocytes in Tgfbr2fl/fl;Wnt1-Cre mice is delayed and they are smaller in size in the condylar process and completely missing in the angular process. TGF-β signaling controls Sox9 expression in the proximal region, because Sox9 expression is delayed in condylar processes and missing in angular process in Tgfbr2fl/fl;Wnt1-Cre mice. Moreover, exogenous TGF-β can induce Sox9 expression in the mandibular arch. In the angular processes of Tgfbr2fl/fl;Wnt1-Cre mice, osteoblast differentiation is accelerated and Dlx5 expression is elevated. Significantly, deletion of Dlx5 in Tgfbr2fl/fl;Wnt1-Cre mice results in the rescue of cartilage formation in the angular processes. Finally, TGF-β signaling-mediated Scleraxis expression is required for tendonogenesis in the developing skeletal muscle. Thus, CNC-derived cells in the proximal region of mandible have a cell intrinsic requirement for TGF-β signaling. 相似文献
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