共查询到20条相似文献,搜索用时 15 毫秒
1.
Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro 总被引:1,自引:0,他引:1
Konrad L Keilani MM Laible L Nottelmann U Hofmann R 《Apoptosis : an international journal on programmed cell death》2006,11(5):739-748
Massive apoptosis of pubertal male germ cells is important for the development of functional spermatogenesis in the adult
testis. Although the trigger(s) for male germ cell loss at puberty remain undefined, we have hypothesized that transforming
growth factor-betas (TGF-βs) play an active role. Here we demonstrate that the three mammalian TGF-β isoforms, TGF-β1, TGF-β2
and TGF-β3, induce distinct apoptosis of pubertal spermatogonia and spermatocytes in a dose-dependent manner. Induction of
male germ cell death by activation of caspase-3 was most pronounced with TGF-β2 compared to TGF-β1 and TGF-β3. Furthermore,
we found colocalization of activated caspase-3 with apoptotic protease-activating factor-1 (Apaf-1) in apoptotic germ cells,
thus indicating the importance of the intrinsic mitochondrial pathway in TGF-β-induced apoptosis. The specificity of the TGF-β
effects was proven by addition of recombinant latency-associated peptide against TGF-β1 (rLAP-TGF-β1) which completely abolished
TGF-β1-induced and TGF-β3-induced germ cell apoptosis. Although TGF-β2-triggered germ cell death also was significantly reduced
by rLAP-TGF-β1, inhibition was not maximal. Our results suggest that the three TGF-β isoforms induce apoptosis of pubertal
male germ cells via the mitochondrial pathway in vitro and are thus likely candidates involved in the excessive first wave of apoptosis of male germ cells during puberty.
Lutz Konrad and Marcel Munir Keilani contributed equally to this work. 相似文献
2.
Méndez C Carrasco E Pedernera E 《Journal of experimental zoology. Part A, Comparative experimental biology》2005,303(3):179-185
The aim of the present study was to evaluate the effect of hypophysectomy on cell proliferation in the left ovary and the left testis of 8- to 14-day-old chick embryos. Hypophysectomy was performed by the partial decapitation technique. At 44-46 h of incubation, chick embryo heads were sectioned at the mesencephalic level and the prosencephalic region removed. Embryos were further incubated until 8-14 days of development. Cell division was evaluated by bromodeoxyuridine (BrdU) incorporation and by counting the total number of somatic and germ cells in the gonads. The ovary displayed an exponential increase in the number of somatic and germ cells and a higher rate of BrdU incorporation compared to the testis. BrdU incorporation was reduced in the ovary of hypophysectomized embryos at 9-14 days of incubation, while in the testis, the reduction was significant at 14 days of development. Changes in the total number of somatic and germ cells further suggest that the absence of hypophysis affects the growth of the ovary earlier than the growth of the testis. Reduction in the number of somatic and germ cells after hypophysectomy in the ovary was reversed by a hypophyseal graft on the chorioallantoic membrane. The adenohypophysis regulates, probably through gonadotropic hormones, proliferation of somatic and germ cells in the gonads during chick embryo development. 相似文献
3.
4.
5.
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
6.
Conditioned medium from adipose derived stem cells (ADSC-CM) stimulates both collagen synthesis and migration of fibroblasts,
and accelerates wound healing in vivo. Recently, the production and secretion of growth factors has been identified as an
essential function of adipose-derived stem cells (ADSCs). However, the main soluble factor of ADSC-CM which mediates paracrine
effects and its underlying mechanism has not been elucidated yet. In this study, we considered transforming growth factor-beta1
(TGF-β1) as a strong candidate for paracrine effect of ADSC-CM and investigated collagen synthesis and hyaluronic acid synthase
(HAS) expression. After ADSC-CM addition, collagen type I, type III, HAS and hyaluronic acid (HA) expressions on human dermal
fibroblasts (HDFs) were evaluated. Furthermore, to clarify effects of TGF-β1 as a paracrine mediator, TGF-β1 antibody and
external supplementary TGF-β1 were treated to HDFs. Collagens type I, type III, HAS-1 and HAS-2 mRNA expressions of HDFs were
greatly increased by ADSC-CM treatment, however there was no change in TGF-β1 antibody treated HDFs compared with non-treated
control. These results strongly demonstrate that TGF-β1 plays an important role as a paracrine mediator of ECM synthesis.
The fact that TGF-β1 contained in ADSC-CM not only accelerates collagen deposition but also increase hyaluronic acid synthesis
of HDFs through HAS-1 and HAS-2 expression was also elucidated in this study. Therefore, ADSC-CM shows promise for the treatment
of cutaneous wounds and accelerates granulation formation during healing process. 相似文献
7.
TGFβ signalling in the development of ovarian function 总被引:1,自引:0,他引:1
Drummond AE 《Cell and tissue research》2005,322(1):107-115
Ovarian development begins back in the embryo with the formation of primordial germ cells and their subsequent migration and colonisation of the genital ridges. Once the ovary has been defined structurally, the primordial germ cells transform into oocytes and become housed in structures called follicles (in this case, primordial follicles), a procedure that, in most mammals, occurs either shortly before or during the first few days after birth. The growth and differentiation of follicles from the primordial population is termed folliculogenesis. Primordial follicles give rise to primary follicles that transform into preantral follicles, then antral follicles (secondary follicles) and, finally (preovulatory) Graafian follicles (tertiary follicles) in a co-ordinated series of transitions regulated by hormones and local intraovarian factors. Members of the transforming growth factor-β (TGFβ) superfamily have been shown to play important roles in this developmental process starting with the specification of primordial germ cells by the bone morphogenetic proteins through to the recruitment of primordial follicles by anti-Mullerian hormone and, potentially, growth and differentiation factor-9 (GDF9) and, finally, their transformation into preantral and antral follicles in response to activin and TGF-β. Developmental and mutant mouse models have been used to show the importance of this family of growth factors in establishing the first wave of folliculogenesis.The author thanks the NHMRC of Australia for funding (Regkey 241000). 相似文献
8.
9.
In mammals, the primordial follicle pool represents the entire reproductive potential of a female. The transforming growth factor-β (TGF-β) family member activin (ACT) contributes to folliculogenesis, although the exact mechanism is not known. The role of FST288, the strongest ACT-neutralizing isoform of follistatin (FST), during cyst breakdown and primordial follicle formation in the fetal mice ovary was assessed using an in vitro culture system. FST was continuously expressed in the oocytes as well as the cuboidal granulosa cells of growing follicles in perinatal mouse ovaries. Treatment with FST288 delayed germ cell nest breakdown, particularly near the periphery of the ovary, and dramatically decreased the percentage of primordial follicles. In addition, there was a dramatic decrease in proliferation of granulosa cells and somatic cell expression of Notch signaling was impaired. In conclusion, FST288 impacts germ cell nest breakdown and primordial follicle assembly by inhibiting somatic cell proliferation. 相似文献
10.
Corporeau C Groisillier A Jeudy A Barbeyron T Fleury E Fabioux C Czjzek M Huvet A 《Marine biotechnology (New York, N.Y.)》2011,13(5):971-980
The transforming growth factor (TGF)-β superfamily is a group of important growth factors involved in multiple processes such
as differentiation, cell proliferation, apoptosis and cellular growth. In the Pacific oyster Crassostrea gigas, the oyster gonadal (og) TGF-β gene was recently characterized through genome-wide expression profiling of oyster lines selected to be resistant or susceptible
to summer mortality. Og TGF-β appeared specifically expressed in the gonad to reach a maximum when gonads are fully mature, which singularly contrasts
with the pleiotropic roles commonly ascribed to most TGF-β family members. The function of og TGF-β protein in oysters is
unknown, and defining its role remains challenging. In this study, we develop a rapid bacterial production system to obtain
recombinant og TGF-β protein, and we demonstrate that og TGF-β is processed by furin to a mature form of the protein. This
mature form can be detected in vivo in the gonad. Functional inhibition of mature og TGF-β in the gonad was conducted by inactivation
of the protein using injection of antibodies. We show that inhibition of og TGF-β function tends to reduce gonadic area. We
conclude that mature og TGF-β probably functions as an activator of germ cells development in oyster. 相似文献
11.
Liver fibrosis occurs in most types of chronic liver diseases and is characterized by excessive accumulation of extracellular
matrix proteins, leading to disruption of tissue function and eventually organ failure. Transforming growth factor (TGF)-β
represents an important pro-fibrogenic factor and aberrant TGF-β action has been implicated in many disease processes of the
liver. Endoglin is a TGF-β co-receptor expressed mainly in endothelial cells that has been shown to differentially regulates
TGF-β signal transduction by inhibiting ALK5-Smad2/3 signalling and augmenting ALK1-Smad1/5 signalling. Recent reports demonstrating
upregulation of endoglin expression in pro-fibrogenic cell types such as scleroderma fibroblasts and hepatic stellate cells
have led to studies exploring the potential involvement of this TGF-β co-receptor in organ fibrosis. A recent article by Meurer
and colleagues now shows that endoglin expression is increased in transdifferentiating hepatic stellate cells in vitro and
in two different models (carbon tetrachloride intoxication and bile duct ligation) of liver fibrosis in vivo. Moreover, they
show that endoglin overexpression in hepatic stellate cells is associated with enhanced TGF-β-driven Smad1/5 phosphorylation
and α-smooth muscle actin production without altering Smad2/3 signaling. These findings suggest that endoglin may play an
important role in hepatic fibrosis by altering the balance of TGF-β signaling via the ALK1-Smad1/5 and ALK-Smad2/3 pathways
and raise the possibility that targeting endoglin expression in transdifferentiating hepatic stellate cells may represent
a novel therapeutic strategy for the treatment of liver fibrosis. 相似文献
12.
Nader Rahimi Eric Tremblay Laura McAdam Anita Roberts Bruce Elliott 《In vitro cellular & developmental biology. Animal》1998,34(5):412-420
Summary We have developed an in vitro system to examine the influence of adipocytes, a major mammary stromal cell type, on the growth of a murine mammary carcinoma,
SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor, hepatocyte growth factor, which strongly
stimulates proliferation of SP1 cells. We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which inhibit
DNA synthesis in SP1 cells. In addition, latent inhibitory activity is present in conditioned media (CM) from both pre-adipocytes
and adipocytes, and is activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild type epithelial cells,
but not DR27 mutant epithelial cells which lack TGF-β type II receptor. Inhibitory activity of CMs was partially abrogated
by neutralizing anti-TGF-β1 and anti-TGF-β2 antibodies, and was removed following ultrafiltration through membranes of 10
000 Mr but not 30 000 Mr pore size. These results show that the inhibitory effect on DNA synthesis is mediated by TGF-β1-like and TGF-β2-like molecules.
In addition, acid-treated CM as well as purified TGF-β inhibited differentiation of pre-adipocytes. Untreated pre-adipocyte
CM, but not mature adipocyte CM, spontaneously inhibited adipocyte differentiation. Together, these findings indicate that
pre-adipocytes spontaneously activate their own secreted TGF-β, whereas mature adipocytes do not, and suggest that activation
of TGF-β has a potent negative regulatory effect on adipocyte differentiation and tumor growth. Thus, TGF-β may be an important
modulator of tumor growth and adipocyte differentiation via both paracrine and autocrine mechanisms. These findings emphasize
the importance of adipocyte-tumor interactions in the regulation of tumor microenvironment. 相似文献
13.
14.
Pan JJ Chang WJ Barone TA Plunkett RJ Ostrow PT Greenberg SJ 《Cancer immunology, immunotherapy : CII》2006,55(8):918-927
The role that transforming growth factor β1 (TGF-β1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-β1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF-β1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-β1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF-β1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-β1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-β receptor. Cells expressing high levels of truncated TGF-β receptor were less sensitive to TGF-β1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF-β1. These results also would tend to support the possibility that TGF-β1 may be useful in treating some high-grade gliomas. 相似文献
15.
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
16.
Transforming growth factor (TGF-β) plays a pivotal role in angiogenesis. The purpose of this study was to explore the microRNA-mediated regulation of TGF-β receptor-II (TGFBR2) expression during rapid antler growth and proliferation of antler cells in sika deer. Deep sequencing–based expression analysis of miRNAs on the antler tip tissue was performed. Then, two bioinformatics software were used to analyze TGFBR2 3′-UTR sequence for predicting the matched and differentially expressed miRNAs in different tissues of the antler. The results indicated that miRNA-19a and miRNA-19b exhibited the highest upregulation among differentially expressed miRNAs. We also found that the TGFBR2 3′-UTR contains a binding site for miRNA-19a and miRNA-19b by transfection of wild-type and mutant dual-luciferase reporter vectors into antler cartilage cells. Meanwhile, overexpression of miRNA-19a and miRNA-19b significantly inhibited the proliferation of cartilage cells in vitro, and decreased the expression level of TGFBR2 protein. Furthermore, the expression levels of insulin-like growth factor 1 (IGF-1) and TGF-β2, which were associated with TGFBR2, reduced after transfection of cartilage cells with miRNA-19a and miRNA-19b. Our results indicate the significant roles of miRNA-19a and miRNA-19b in proliferation of antler cells and its potential application. 相似文献
17.
Robert W. Wrenn Claire L. Raeuber Lee E. Herman Wendy J. Walton Thomas H. Rosenquist 《In vitro cellular & developmental biology. Animal》1993,29(1):73-78
Summary Transforming growth factor-beta (TGF-β), an ubiquitous regulatory peptide, has diverse effects on the differentiation and
behavior of vascular smooth muscle cells (VSMC). However, the molecular mechanism through which TGF-α exerts its effects remains
obscure. We investigated the phosphoinositide/protein kinase C [PKC] signaling pathway in the action of TGF-β on cultured
embryonic avian VSMC of differing lineage: a) thoracic aorta, derived from the neural crest; and b) abdominal aorta, derived
from mesenchyme. The second messenger responsible for activation of PKC is sn-1,2-diacylglycerol [DAG]; TGF-β increased the
mass amounts of DAG in the membranes of neural crest-derived VSMC concurrent with translocation of PKC from the soluble to
the membrane fraction, but TGF-β had no effect on the DAG or PKC of mesenchyme-derived VSMC. TGF-β potentiated the growth
of platelet-derived growth factor (PDGF)-treated, neural crest-derived VSMC; but abolished PDGF-induced growth of mesenchymal
cells. It is concluded that molecular and functional responses of VSMC to TGF-β are heterogeneous and are functions of the
embryonic lineage of the VSMC. 相似文献
18.
Effects of representative members of the transforming growth factor-β (TGF-β) family, TGF-β1, activin A and BMP-2, on melanin
content and expression of pigment-producing enzymes were examined in B16 melanoma cells. Treatment with TGF-β1 or activin
A but not with BMP-2 significantly decreased melanin content and expression of Tyrosinase and Tyrp-1, suggesting an inhibitory effect of TGF-β1 and activin A on melanin synthesis. TGF-β1 completely inhibited melanin synthesis
induced by α-melanin stimulating hormone (α-MSH), whereas activin A only slightly did. As compared with parental B16 cells,
the inhibitory effects of TGF-β1 and activin A on melanin content were relative smaller in B16 F10 cells, a subline of B16
cells that contain more pigment. The present study indicates that in addition to TGF-β, activin negatively regulates melanogenesis
in the absence of α-MSH, but that the activity in the presence of α-MSH was slightly different between TGF-β and activin. 相似文献
19.
A milk growth factor extract reduces chemotherapeutic drug toxicity in epithelial cells in vitro 总被引:1,自引:0,他引:1
Summary Transforming growth factor-β (TGF-β) and insulin-like growth factor (IGF-I) can attenuate drug-induced cell death in epithelial
cells. Since milk whey contains a mixture of these and other growth factors, we evaluated mitogenic bovine whey extract (MBWE)
for protective activity against chemotherapy drug damage in cultured epithelial cells (mink lung, Mu1.Lu). Etoposide and vinblastine
reduced cell survival by up to 90%. This was attenuated by the addition of MBWE before and during drug exposure, but not following
drug removal. MBWE was compared with individual growth factors known to be present in the mixture. IGF-I and platelet-derived
growth factor were ineffective, whereas TGF-β2 induced growth inhibition and cell survival, with a maximum response at 3 ng/ml.
TGF-β2 bioactivity was also demonstrated by showing that acidification of MBWE (A-MBWE), to activate TGF-β2, enhanced its
growth inhibitory and chemoprotective activities 60- and 12-fold, respectively. However, MBWE contained additional protective
factors. When TGF-β2 and the MBWE preparations were compared, on the basis of growth inhibition equivalents, MBWE protected
cells against drug toxicity at concentrations an order of magnitude lower than with TGF-β2 or A-MBWE. Immunoneutralization
of the TGF-β present in MBWE and A-MBWE eliminated all growth inhibitory activity but not all cell survival activity. We conclude
that the MBWE preparations are cytoprotective against two chemotherapy drugs when added before and during drug exposure. TGF-β
contributes to this activity, but the extracts contain other factors that promote the survival of epithelial cells after chemotherapy
drug exposure. 相似文献
20.
Donald J. Sarubbi Ramaswamy Narayanan Nitin T. Telang Michael J. Newman 《In vitro cellular & developmental biology. Plant》1990,26(12):1195-1201
Summary Novel or modified serum-free media were developed for the anchorage-dependent growth of nontransformed murine mammary epithelial
cells (MMEC) and Balb/MK murine keratinocytes respectively. Growth rates for both cell lines were similar in serum-containing
and serum-free media. The serum-free media were used to evaluate potential mechanisms of epithelial cell growth regulation
by type 1 transforming growth factor β(TGF-β1). The growth of MMEC and Balb/ MK cells was reversibly inhibited 40–65% in a
time- and dose-dependent fashion by TGF-β1 under both serum-containing and serum-free conditions. Constitutive over-expression
of a stranfected c-myc oncogene inMMEC did not result in loss of sensitivity to growth inhibition by TGF-β1. In addition, Balb/MK and MMEC growth
inhibition by TGF-β1 was not potentiated by polynsaturated fatty acids or reversed by vitamin E. Expgenous type V collagen
was able to mimic the inhibitory effects of TGF-β1 on the serum-free growth of Balb/MK and MMEC. In contrast, collagen type
I and IV, fibronectin and laminin did not inhibit the growth of these cells. The type V collagen used was not contaminated
with TGF-β, and subsaturating, but not saturating concentrations of type V collagen and TGF-β1 were additive with respect
to Balb/MK and MMEC growth inhibition. These results demonstrate that nontransformed epithelial cell growth inhibition by
TGF-β1 is mediated by mechanisms distinct from those observed with certain carcinoma and melanoma cells. Our results also
suggest the possible involvement of type V collagen in Balb/MK and MMEC growth inhibition by TGF-β1.
This work was supported, in part, by grant #R29 CA 44741 from the National Institutes of Health, Bethesda, MD to NTT. 相似文献