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PubMedDate not supplied

Collagen fiber orientation as quantified by small angle light scattering in wounds treated with transforming growth factor-beta2 and its neutalizing antibody.

The purpose of this study was determine quantitative differences in collagen fiber orientation in a wound healing model in the presence of transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 antibody. Full-thickness wounds were made in the paravertebral area of two young pigs. Wounds were treated once, topically, with either transforming growth factor-beta2 or anti-transforming growth factor-beta2 antibody, or with methylcellulose gel. Control wounds were left untreated. Tissue biopsies were obtained from each wound on days 7, 14 and 46 post wounding. Tissue sections were stained with hematoxylin and eosin, and collagen fiber preferred orientation was quantified using small angle light scattering. Our results indicated that wounds treated with transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 antibody had a significantly higher degree of orientation of collagen fibers than normal unwounded skin on days 7, 14 and 46 (p < 0.001). Transforming growth factor-beta2- treated wounds had a higher degree of orientation of collagen fibers than control wounds on days 7 and 14 (p < 0.001), and control wounds displayed a higher degree of orientation than wounds treated with anti-transforming growth factor-beta2,3 and normal unwounded skin at all time points (p < 0.001). These results suggest that differences in the dermal collagen degree of orientation correlate with scarring, and show that small angle light scattering can be used quantitatively to assess differences in the collagen fiber architecture of dermal wounds.

Administration, Topical↗

PubMed2004

17Beta-estradiol confers a protective effect against transforming growth factor-beta2-induced cataracts in female but not male lenses.

Transforming growth factor-beta2 (TGF-beta2) induces anterior subcapsular cataracts, with a marked increase in cytoskeletal and extracellular matrix proteins, such as alpha-smooth muscle actin (alphaSMA). It has been shown that 17beta-estradiol (E2) can prevent TGF-beta2-induced cataracts in lenses from ovariectomized female rats. The purpose of the current study was to extend this finding by testing whether E2 can prevent TGF-beta2-induced cataracts and inhibit the induction of alphaSMA gene expression in normal male and normal, non-ovariectomized female rats.Sex-specific differences were observed in 17-week-old rat lenses incubated in 0.15 ng ml(-1) TGF-beta2 and in 10(-8)M E2 plus TGF-beta2. TGF-beta2 induced approximately twice as many anterior subcapsular plaques and 1.5 times the level of alphaSMA transcripts in male lenses compared to female lenses. Notably, E2 inhibited plaque formation and the induction of alphaSMA transcripts in female rat lenses but not in male rat lenses. E2 also inhibited the induction of alphaSMA in TGF-beta2-incubated lenses from ovariectomized female rats.E2 prevented lens opacification and the induction of alphaSMA gene expression in female, but not male, lenses. This sex-specific difference may have implications for studies on the therapeutic use of estradiol for treatment of secondary cataract.

Actins↗

PubMed1998

Nondisruptive, in vivo method for biomechanical characterization of linear incision wound healing: preliminary report.

Previous work on in vivo biomechanical characterization of soft tissues and wound healing has led to the development of a methodology for nondisruptive, in vivo biomechanical analysis of linear incision wounds. The purpose of this preliminary study was to define nondisruptive biomechanical parameters that characterize progressive healing and compare them with an in vivo disruptive parameter of ultimate pressure at failure (in vivo strength). Male Sprague-Dawley rats (n = 60), each weighing 250 to 300 gm, were anesthetized and underwent creation of paired full-thickness linear incision wounds. The rats were divided into three groups (n = 10/group per time period): control group, nothing applied to either wound; carrier group, bovine serum albumin applied to each wound; transforming growth factor-beta2 group, transforming growth factor-beta2 in bovine serum albumin applied to each wound. On postoperative days 5 and 10, rats from each group underwent in vivo biomechanical testing using the Dimensional Analysis System (Dimensional Analysis Systems, Inc., Nashville, Tenn.). This computer-driven device integrates a video camera and processor with a vacuum controller, valve, and transducer to provide measurements of tissue deformation (in millimeters) and negative pressure (mmHg) as a multiaxial stress (vacuum) is applied to a wound. On each rat, one incision was tested disruptively and the other incision was tested nondisruptively. Disruptive data were measured as ultimate pressure (mmHg) at failure, or the amount of pressure required to disrupt the wound. Nondisruptive data were measured for tissue stiffness (kiloPascals) during application of negative pressure (maximum, 80 mmHg). On postoperative day 5, wounds treated with transforming growth factor-beta2 had significantly increased in vivo wound strength compared with carrier wounds. The nondisruptive parameter of tissue stiffness was also significantly increased for the transforming growth factor-beta2 treated wounds, thus supporting the disruptive data. On postoperative day 10, there was no difference in mean wound strength or mean tissue stiffness among any of the groups. These preliminary data represent the first report of in vivo, nondisruptive biomechanical characterization of linear incision wounds. The results suggest that through in vivo measurements of tissue stiffness, differences can be detected between treatment groups. Because the healing wound may be characterized without the need for disruption, this methodology should allow for consecutive, in vivo biomechanical testing of wounds in future wound healing studies.

Animals↗

PubMed2000

Transforming growth factor-beta2 mediates mesenchymal-epithelial interactions of testicular somatic cells.

Transforming growth factor-beta2 (TGFbeta2) is an important mediator of growth and differentiation. We here describe for the first time the complete sequence of the TGFbeta2 complementary DNA derived from peritubular myoid cells of the rat testis. The size of the rat TGFbeta2 complementary DNA was 1245 bp, and the deduced protein sequence contained 414 amino acids. Sequence comparison with the human and mouse amino acid sequences demonstrated 96.4% and 97.9% sequence identities, respectively. To elucidate the functional role of TGFbeta2 in testicular somatic cells, we studied its secretion in vitro in monocultures and cocultures of mesenchymal peritubular and epithelial Sertoli cells. The highest amounts of TGFbeta2 protein were secreted in the cocultures and by peritubular cells, whereas Sertoli cells secreted only minor amounts. Stimulation experiments with FSH revealed a reduced secretion of TGFbeta2 in cocultures, probably mediated by a paracrine interaction of the FSH-responsive Sertoli cells. In contrast, TGFbeta2 secretion by peritubular cells was increased after stimulation with glucocorticoids and after addition of recombinant TGFbeta2, indicating an autoregulation of TGFbeta2. Furthermore, application of recombinant TGFbeta2 to cocultures resulted in an enhanced aggregation and cell clustering of Sertoli cells, pointing to an important role of TGFbeta2 in the paracrine interaction of peritubular and Sertoli cells of the developing rat testis.

Amino Acid Sequence↗

PubMed2006

A novel functional polymorphism in the transforming growth factor-beta2 gene promoter and tumor progression in breast cancer.

Transforming growth factor-beta (TGF-beta), a multifunctional growth factor, plays an important role in breast cancer. There is increasing evidence that enhanced expression of TGF-beta promotes breast cancer progression contributing to metastasis and invasiveness of the tumor. We identified a functional polymorphism in the TGFB2 promoter, a 4-bp insertion at position -246 relative to the transcriptional start site (-246ins). Transient transfection experiments showed that the -246ins polymorphism significantly increased TGFB2 promoter activity in breast cancer cells. Electrophoretic mobility shift assays revealed binding of the transcription factor Sp1 to the -246ins allele. Overexpression of Sp1 enhanced promoter activity of the -246ins allele, demonstrating that Sp1 mediates transcriptional activation. Furthermore, the -246ins allele was associated with enhanced TGF-beta(2) expression in breast cancer tissue (P = 0.0005). To evaluate the role of the polymorphism in breast cancer, frequency of the -246ins allele was determined in breast cancer patients (n = 78) and healthy female controls (n = 143). No significant differences were found. However, the presence of the -246ins allele was associated with lymph node metastasis (P = 0.003). The -246ins allele was a significant predictor for lymph node metastasis independent of estrogen and progesterone receptor status in a multivariate logistic regression analysis (P = 0.0118, odds ratio, 5.18; 95% confidence interval, 1.44-18.62). We provide evidence that the TGFB2 -246ins polymorphism leads to enhanced TGF-beta(2) expression levels in vivo and might thereby contribute to tumor progression and development of metastases.

Alleles↗

PubMed1999

Transforming growth factor-beta2 is elevated in skeletal muscle disorders.

The transforming growth factor betas (TGF-betas) are multifunctional growth factors that act on both fibroblasts and myosatellite cells. In rodent models of muscle diseases, high levels of TGF-beta2 are expressed by myogenic cells. We have examined whether the expression of TGF-beta2 is also elevated in diseased human muscles. The disorders examined were Duchenne muscular dystrophy, myotonic dystrophy, myotubular myopathy, spinal muscular atrophy, and amyotrophic lateral sclerosis. The levels of TGF-beta2 immunoreactivity were elevated in atrophic, necrotic, and regenerating fibers and in fibers with central nuclei or cytoplasmic masses, irrespective of whether fibrosis was present. We therefore suggest that TGF-beta2 is important for muscle repair and that the presence of a TGF-beta within a muscle only leads to fibrosis if certain other factors are present.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Transforming growth factor-beta2 enhances differentiation of cardiac myocytes from embryonic stem cells.

Stem cell therapy holds great promise for the treatment of injured myocardium, but is challenged by a limited supply of appropriate cells. Three different isoforms of transforming growth factor-beta (TGF-beta) -beta1, -beta2, and -beta3 exhibit distinct regulatory effects on cell growth, differentiation, and migration during embryonic development. We compared the effects of these three different isoforms on cardiomyocyte differentiation from embryonic stem (ES) cells. In contrast to TGF-beta1, or -beta3, treatment of mouse ES cells with TGF-beta2 isoform significantly increased embryoid body (EB) proliferation as well as the extent of the EB outgrowth that beat rhythmically. At 17 days, 49% of the EBs treated with TGF-beta2 exhibited spontaneous beating compared with 15% in controls. Cardiac myocyte specific protein markers sarcomeric myosin and alpha-actin were demonstrated in beating EBs and cells isolated from EBs. In conclusion, TGF-beta2 but not TGF-beta1, or -beta3 promotes cardiac myocyte differentiation from ES cells.

Animals↗

PubMed2001

Retinoblastoma protein interacts with ATF2 and JNK/p38 in stimulating the transforming growth factor-beta2 promoter.

Two highly related transcription factors, ATF2 and ATFa, enhance the activity of the Transforming Growth Factor beta2 (TGF-beta2) promoter via a partial cAMP response element in transfected CHO cells. The retinoblastoma protein (Rb) also activates this promoter and enhances the stimulatory effects of ATF2 but causes near extinction of the effects of ATFa. The site on Rb required for its effects alone and in combination with the ATFs has been mapped mainly to the A/B pockets but the C pocket is also implicated. Whereas MKK7 or JNK expression enhances the actions of both ATFs, MKK6 or p38 expression only augments the effects of ATF2. Immunoprecipitation with Rb antibodies of lysates from transfected cells brings down expressed ATF2 but not ATFa. Expressed JNK and p38 are also found in the anti-Rb immunoprecipitates. ATF2 antibodies bring down expressed Rb, JNK and p38 and expression of Rb enhances the immunoprecipitation of both JNK and p38 by ATF2 antibodies. The results suggest that Rb is acting as a matchmaker by bridging either JNK or p38 with their common substrate ATF2 and, hence, facilitating its activation. Consistent with this suggestion, expression of Rb enhances the phosphorylation of ATF2 in CHO cells.

Activating Transcription Factor 2↗

PubMed2004

Transforming growth factor-beta2 induces bronchial epithelial mucin expression in asthma.

The transforming growth factor (TGF)-beta family is important for tissue repair in pathological conditions including asthma. However, little is known about the impact of either TGF-beta1 or TGF-beta2 on asthmatic airway epithelial mucin expression. We evaluated bronchial epithelial TGF-beta1 and TGF-beta2 expression and their effects on mucin expression, and the role of TGF-beta1 or TGF-beta2 in interleukin (IL)-13-induced mucin expression. Epithelial TGF-beta1, TGF-beta2, and mucin expression were evaluated in endobronchial biopsies from asthmatics and normal subjects. The effects of TGF-beta1 or TGF-beta2 on mucin MUC5AC protein and mRNA expression, and the impact of IL-13 on epithelial TGF-beta1, TGF-beta2, and MUC5AC were determined in cultured bronchial epithelial cells from endobronchial brushings of both subject groups. In biopsy tissue, epithelial TGF-beta2 expression levels were higher than TGF-beta1 in both asthmatics and normals. TGF-beta2, but not TGF-beta1, was increased in asthmatics compared with normals, and significantly correlated with mucin expression. TGF-beta2, but not TGF-beta1, increased mucin expression in cultured epithelial cells from both subject groups. IL-13 increased the release of TGF-beta2, but not TGF-beta1, from epithelial cells. A neutralizing TGF-beta2 antibody partially inhibited IL-13-induced mucin expression. These data suggest that TGF-beta2 production by asthmatic bronchial epithelial cells may increase airway mucin expression. IL-13-induced mucin expression may occur in part through TGF-beta2 up-regulation.

Adult↗

PubMed2002

Transforming growth factors beta1, beta2 and beta3 and their receptors are differentially expressed in human peritoneal fibroblasts in response to hypoxia.

PROBLEM: Little is known about the role of peritoneal fibroblasts in adhesion formation. This study determines the effect of hypoxia and transforming growth factor (TGF)-beta1 treatment on the expression of TGF-beta1-3 and TGF-betaI and betaII receptors in human peritoneal fibroblasts (HPF). TGF-beta isoforms and their receptors have been implicated as mediators of the healing process and adhesion development. METHODS: HPF were cultured under normal and hypoxic condition, and treated with and without (1 ng/mL) TGF-beta1 for 24 hr. Total RNA from each group was subjected to multiplex reverse transcriptase-polymerase chain reaction (RT/PCR) to quantitate TGF-beta1-3 and TGF-betaI and betaII receptors messenger RNA (mRNA) levels. RESULTS: Hypoxia resulted in a significant increase in TGF-beta1 (26%; P < 0.05), TGF-betaIR (34%; P < 0.05) and TGF-betaIIR (29%; P < 0.05) mRNA levels, with no effect on TGF-beta2 or beta3. TGF-beta1 treatment resulted in a significant increase in TGF-beta1 (35%; P < 0.05), but a decrease in TGF-beta2 (22%; P < 0.05) and no effect on TGF-beta3, TGF-betaIR or TGF-betaIIR. Combined treatment of hypoxia and TGF-beta1 caused a significant increase in TGF-beta1 (37%; P < 0.05), TGF-beta2 (12%; P < 0.05), TGF-betaIR (32%; P < 0.05) and TGF-betaIIR (34%; P < 0.05). There is no significant change in the mRNA levels of TGF-beta3 in any of the treatments. CONCLUSION: Hypoxia and TGF-beta1 treatments of cultured HPF modulate the expression of TGF-beta1, beta2 and beta3 and their receptors betaIR and betaIIR by increasing the ratio of TGF-beta1 and beta2 to beta3, thus favoring the development of peritoneal adhesion.

Activin Receptors, Type I↗

PubMed2000

Induction of endochondral bone formation by recombinant human transforming growth factor-beta2 in the baboon (Papio ursinus).

Members of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic and osteogenic proteins (BMPs/OPs) but not the TGF-beta proteins themselves, induce endochondral bone formation in vivo, when implanted in extraskeletal heterotopic sites of rodents. Here we show that recombinant human TGF-beta2 (hTGF-beta2) induces endochondral bone formation 30 days after implantation in heterotopic intramuscular sites of the baboon (Papio ursinus) at doses of 1, 5 and 25 microg per 100 mg of guanidinium-inactivated collagenous bone matrix as carrier. On day 90 there was generation of large radiopaque and corticalized intramuscular ossicles. Five and 25 microg hTGF-beta2 induced large ossicles in the rectus abdominis of the primate as evaluated by key parameters of bone formation, including generated tissue area, mineralized bone and osteoid volumes, and tissue alkaline phosphatase activity. On day 30 and 90 after healing, hTGF-beta2 also induced bone formation when implanted in the rectus abdominis in conjunction with a sintered porous hydroxyapatite as carrier. mRNA expression in tissues from heterotopic specimens showed OP-1 (BMP-7) and BMP-3 transcripts in low abundance and with a linear dose-dependent increase both in collagenous matrix and hydroxyapatite samples. Type IV collagen mRNA expression, a marker of angiogenesis, was stronger in collagenous than hydroxyapatite samples. Growth and differentiation factor-10 (GDF-10) mRNA transcripts were expressed in ossicles with a distinctly chondrogenic phase, but its expression was greater in ossicles generated in porous hydroxyapatites, in which bone formation is not via a chondrogenic phase, but is rather intramembranous, without expression of type II collagen mRNA. In the same animals, however, 10 and 100 microg of the recombinant morphogen delivered by identical carriers (collagenous matrix and sintered hydroxyapatite) failed to heal calvarial defects. Thus in the primate, TGF-betas themselves are inducers of endochondral bone formation, although the present data strongly indicate that the bone inductive activity of hTGF-beta2 is site and tissue specific, since a single application of hTGF-beta2, or hTGF-beta1 in previously published experiments, did not induce bone in calvarial defects, but did induce endochondral bone differentiation in heterotopic sites.

Animals↗

PubMed2001

Specific inhibition of transforming growth factor-beta2 expression in human osteoblast cells by antisense phosphorothioate oligonucleotides.

To elucidate the role of endogenous transforming growth factor (TGF)-beta2 on human osteoblast cell, antisense phosphorothioate oligonucleotides (S-ODNs) complementary to regions in mRNA of TGF-beta2 were synthesized and examined their effects on TGF-beta2 production and cell proliferation in a human osteoblast cell line ROS 17/2. Antisense S-ODNs were designated for three different target regions in the mRNA of TGF-beta2. Among several antisense S-ODN analyzed, an oligonucleotide (AS-11) complementary to the translation initiation site of mRNA of TGF-beta2 demonstrated a selective and strong inhibitory effect on TGF-beta2 production in osteoblast cells. Other antisense S-ODNs which were designated for other regions in mRNA of TGF-beta2 and one- or three-base mismatched analogs of AS-11 showed little or much less antisense activities than AS-11. Therefore, the most effective target site in mRNA of TGF-beta2 is at the initiation codon region. The antisense effects of AS-11 were observed without reduction of levels of mRNA of TGF-beta2. Furthermore, the inhibition of TGF-beta2 expression by antisense S-ODN appeared to enhance cell proliferation, demonstrating the growth inhibitory effect of autocrine TGF-beta2 in osteoblast cells.

Blotting, Northern↗

PubMed2007

Transforming growth factor-beta2 modulates synaptic efficacy and plasticity and induces phosphorylation of CREB in hippocampal neurons.

Transforming growth factor-betas (TGF-betas) are widely expressed and play roles as multifunctional growth factors and regulators of key events in development, disease, and repair. However, it is not known whether TGF-betas affect the plasticity of hippocampal neurons. As a first step to address this issue, we examined whether TGF-beta2 modulated the electrophysiological and biochemical properties of cultured hippocampal neurons. We found that prolonged 24 h treatment with TGF-beta2 induced facilitation of evoked postsynaptic currents (ePSCs). This facilitation was associated with a decrease in short-term synaptic depression of ePSCs and increases in both the amplitude and frequency of spontaneous miniature postsynaptic currents (mPSCs). The long-term changes of ePSCs and mPSCs may be associated with cAMP response element-binding protein (CREB), which has been previously implicated in long-term potentiation. Immunofluorescence techniques and Western blot analysis both revealed that TGF-beta2 enhanced the phosphorylation of CREB. Together, these results suggest that TGF-beta2 may play a role in the cascade of events underlying long-term synaptic facilitation in hippocampus, and that CREB may be an important mediator of these effects.

Analysis of Variance↗

PubMed1998

Interferon-gamma antagonizes transforming growth factor-beta2-mediated immunosuppression in murine Toxoplasma encephalitis.

The in vivo modulating activity of recombinant transforming growth factor (TGF)-beta2 on acute toxoplasmosis was evaluated in both Toxoplasma gondii susceptible C57BL/6 and resistant BALB/c mice. TGF-beta2 lethally exacerbated Toxoplasma encephalitis in C57BL/6, but not in BALB/c mice. In C57BL/6 mice, TGF-beta2 induced a profound dose-dependent increase of the intracerebral parasitic load as well as a reduction of IFN-gamma levels in serum and cerebrospinal fluid with a coincident decrease of MHC class II antigen expression of macrophages, microglial cells, and B cells. Furthermore, TGF-beta2-treated C57BL/6 mice showed a reduced activation of CD4+ and CD8+ T cells and a diminished recruitment of immune cells to the brain. The TGF-beta2-mediated development of lethal toxoplasmosis in C57BL/6 mice was abolished by treatment with recombinant interferon (IFN)-gamma.

Animals↗

PubMed2002

Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2.

Recently, we have reported that the cytokines alpha-melanocyte-stimulating hormone (alpha-MSH) and transforming growth factor-beta2 (TGF-beta2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used alpha-MSH and TGF-beta2 to generate ocular autoantigen-specific Treg cells and adoptively transferred them into mice susceptible to experimental autoimmune uveoretinitis (EAU), there was suppression in the incidence and severity of EAU. Specificity to a retinal autoantigen was required for the Treg cells to suppress EAU. When stimulated, these Treg cells produced TGF-beta1, and their production of interferon-gamma, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that alpha-MSH with TGF-beta2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immunomodulating cytokines to purposely induce antigen-specific Treg cells to prevent and suppress autoimmune disease.

Adoptive Transfer↗

PubMed2003

Transforming growth factor-beta2 inhibition of corneal endothelial proliferation mediated by prostaglandin.

PURPOSE: To determine the influence of Prostaglandin (PG) E2 on transforming growth factor (TGF)-beta2-mediated inhibitory effects on the proliferation of corneal endothelial cells (CE). METHODS: The PGE2 and cell proliferation assays were performed using cultured rabbit corneal endothelium. A PGE2-specific enzyme immunoassay was used to check PGE2 synthesis in supernatants of cells cultured with and without added TGF-beta2 and/or indomethacin. To evaluate the inhibitory effects of PGE2 and TGF-beta2 on CE proliferation, the number of cells grown with exogenous PGE2, or TGF-beta2 with or without indomethacin pretreatment was determined. RESULTS: TGF-beta2, 0.5 to 50 ng/ml, increased the PGE2 secretion of CE dose-dependently in a time-dependent manner. Indomethacin (> or =0.1 microg/ml) inhibited this PGE2 secretion to a low level (around 5-10 ng/ml) in the presence or absence of exogenous TGF-beta2. Both exogenous TGF-beta2 and PGE2 inhibited CE proliferation dose-dependently over a wide range of concentrations. Indomethacin reversed the inhibitory effects of TGF-beta2 but not those of exogenous PGE2. In the medium supplemented with indomethacin, even in the presence of 50 ng/ml of TGF-beta2, CE growth did not differ from control cultures. CONCLUSIONS: TGF-beta2 stimulates PGE2 synthesis in CE and inhibits CE proliferation in a dose-dependent manner. Indomethacin extinguishes the inhibitory effects of TGF-beta2 on CE proliferation but not the effect of exogenous PGE2. These data suggest that the antiproliferative effects of TGF-beta2 on CE may be possibly due to TGF-beta2-induced synthesis of PG, most likely PGE2. SUMMARY: Inhibition of endogenous prostaglandins synthesis by indomethacin extinguished the inhibitory effects of Transforming Growth Factor-beta2 on corneal endothelium proliferation but not exogenous prostaglandin E2. It suggesting that TGF-beta2-induced autocrine synthesis of PGs, most likely PGE2, may be responsible for the anti-proliferative effects of TGF-beta2 on corneal endothelium.

Animals↗

PubMed2004

Effect of human papillomavirus type 16 E6 and E7 oncogenes on the activity of the transforming growth factor-beta2 (TGF-beta2) promoter.

The effect of the human papillomavirus type 16 (HPV 16) E6 and E7 proteins was studied on the transcriptional activity of the human transforming growth factor beta2 (TGF-beta) promoter in different cell lines. Luciferase tests were performed after co-transfection of cells with TGF-beta2 reporter constructs and HPV 16 E6 or E7 expression vectors. HPV 16 E7, but not E6 significantly repressed TGF-beta2 promoter activity in NIH/3T3 cells, which have wild-type p53 and pRb proteins. The repressive effect of HPV 16 E7 on the transcriptional activity of the TGF-beta2 promoter could be localized to the promoter region -528 to -251 relative to the transcriptional start site. Ability of E7 to bind pRb was necessary to inhibit the TGF-beta2 promoter. Over-expression of the transcription factor E2F-1 had an effect on the TGF-beta2 promoter similar to that of E7, which may indicate that HPV 16 E7 represses the TGF-beta2 promoter by releasing E2F from pRb.

3T3 Cells↗

PubMed1996

Transforming growth factor-beta2-mediated regulation of C3 gene expression in monocytes.

In this report, we show that transforming growth factor-beta2 (TGF-beta2) regulates C3 gene expression in the human monocyte cell lines, U937 and THP-1, and human peripheral blood monocytes. Treatment of U937 or THP-1 cells with TGF-beta2 resulted in a dose-dependent induction of C3 protein and mRNA expression. Dose-dependent increases of C3 protein and mRNA levels were also detected in TGF-beta2-treated primary blood monocytes, demonstrating that TGF-beta2 can modulate C3 expression in nontransformed monocytes. Kinetic analysis demonstrated that TGF-beta2-mediated induction of C3 mRNA and protein could be detected within 8 hr, and the induction was continuous up to 72 hr. Exposure of cells to TGF-beta2 for as little as 2 hr was sufficient to induce C3 expression. TGF-beta2 did not significantly increase C3 mRNA stability as determined by mRNA half-life studies. Collectively, our results demonstrate that TGF-beta2 regulates the expression of C3 in monocytes and suggest that TGF-beta2 may play a role in modulating the synthesis of C3 during inflammatory responses.

Cell Line↗