SEARCH · PubMed Health

Results for “Transforming Growth Factor beta1”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1999

Possible involvement of bcl-2 in regulation of cell-cycle progression of haemopoietic cells by transforming growth factor-beta1.

Transforming growth factor-beta1 (TGF-beta1) acts directly on haemopoietic progenitor cells to regulate their growth. To investigate a possible link between the action of TGF-beta1 and cell death regulators such as bcl-2, we utilized Ba/F3 cells, the interleukin-3 (IL-3)-dependent growth of which could be modulated by TGF-beta1, as well as haemopoietic progenitor cells. We demonstrate here that up-regulation of bcl-2 protein (Bcl-2) as well as that of an inhibitor of cyclin/cyclin-dependent kinase complex, p27, was associated with TGF-beta1-induced deceleration of the cell-cycling of haemopoietic progenitor cells and Ba/F3 cells. The data from cell-cycle analysis of Ba/F3 cells showed that TGF-beta1 retarded the G1 to S phase transition. Analysis of cells with the potential to express Bcl-2 in an inducible manner indicated that up-regulation of Bcl-2 was sufficient for not only an increase in the level of p27 but also to inhibit the cell growth. Using c-kit-overexpressing cells, we observed that the potential of TGF-beta1 to up-regulate the expression of Bcl-2 and p27 could be counteracted by the c-kit ligand, stem cell factor. These results demonstrate that Bcl-2 exerts an essential function in the regulation of G1 to S phase transition of haemopoietic cells by TGF-beta1.

Animals↗

PubMed2001

Pax-8 is essential for regulation of the thyroglobulin gene by transforming growth factor-beta1.

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that is thought to play a major role in the regulation of growth and differentiation of thyroid cells. However, little is known of its detailed mechanisms of action in thyrocytes. We have therefore studied the molecular mechanisms of TGF-beta1 action on thyroglobulin (TG) gene expression by focusing our attention on TGF-beta1 regulation of thyroid-specific transcription factors. TGF-beta1 decreased TG messenger RNA (mRNA) expression both in the presence and in the absence of TSH in rat thyroid FRTL-5 cells. Transfected into FRTL-5 cells, the activity of reporter plasmids containing the rat TG promoter ligated to a luciferase gene was significantly suppressed by the addition of TGF-beta1. When the nuclear extracts prepared from TGF-beta1-treated FRTL-5 cells were used in gel mobility shift assays, the amount of protein-DNA complex formed by Pax-8 was reduced, both in the presence and in the absence of TSH, but protein-DNA complexes formed by thyroid transcription factor-1 (TTF-1) and TTF-2 were not. The suppressive effect of TGF-beta1 on Pax-8/DNA complex formation is in part due to the suppression of Pax-8 mRNA and protein levels by TGF-beta1. Expressions of Pax-8 mRNA and protein, which were assessed by Northern blot and Western blot analyses, respectively, were decreased by TGF-beta1 treatment of FRTL-5 cells in a concentration-dependent manner. In a transfection experiment, mutation of the Pax-8-binding site caused a loss of both TGF-beta1- and TSH-responsiveness in TG promoter activity. Overexpression of Pax-8 abolished the TGF-beta1 suppression of TG promoter activity. These results indicate that TGF-beta1 decreases Pax-8 mRNA levels as well as Pax-8 DNA-binding activity, which, at least in part, seems to be involved in the TGF-beta1-induced suppression of TG gene expression.

Animals↗

PubMed1998

The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1.

Transforming growth factor-beta1 (TGFbeta1), a major promoter of myofibroblast differentiation, induces alpha-smooth muscle (sn) actin, modulates the expression of adhesive receptors, and enhances the synthesis of extracellular matrix (ECM) molecules including ED-A fibronectin (FN), an isoform de novo expressed during wound healing and fibrotic changes. We report here that ED-A FN deposition precedes alpha-SM actin expression by fibroblasts during granulation tissue evolution in vivo and after TGFbeta1 stimulation in vitro. Moreover, there is a correlation between in vitro expression of alpha-SM actin and ED-A FN in different fibroblastic populations. Seeding fibroblasts on ED-A FN does not elicit per se alpha-SM actin expression; however, incubation of fibroblasts with the anti-ED-A monoclonal antibody IST-9 specifically blocks the TGFbeta1-triggered enhancement of alpha-SM actin and collagen type I, but not that of plasminogen activator inhibitor-1 mRNA. Interestingly, the same inhibiting action is exerted by the soluble recombinant domain ED-A, but neither of these inhibitory agents alter FN matrix assembly. Our findings indicate that ED-A-containing polymerized FN is necessary for the induction of the myofibroblastic phenotype by TGFbeta1 and identify a hitherto unknown mechanism of cytokine-determined gene stimulation based on the generation of an ECM-derived permissive outside in signaling, under the control of the cytokine itself.

Actins↗

PubMed1998

Expression of transforming growth factor-beta1 and transforming growth factor-beta Type-II receptor mRNA in papillary thyroid carcinoma.

Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of epithelial cell proliferation. Signal transduction by TGF-beta1 involves direct binding to the TGF-beta Type-II receptor and then the formation of a heterodimeric complex of TGF-beta Type-I and Type-II receptor. To explore the role of TGF-beta1 in thyroid carcinoma, we examined the expression of TGF-beta1 and TGF-beta Type-II receptor mRNA by northern blotting analysis in both 14 papillary thyroid carcinomas and surrounding normal thyroid tissues. Relative mRNA level was determined by scanning densitometry of the autoradiogram and corrected for loading differences using a human beta-actin cDNA probe. The relative mRNA levels of TGF-beta1 in 12 out of 14 papillary thyroid carcinomas were higher than those in surrounding normal thyroid tissues. In contrast, the relative mRNA levels of TGF-beta Type-II receptor were reduced to 60.1+/-18.3% of those of normal thyroid tissues in 10 papillary thyroid carcinomas. There were no clear relationships between the relative mRNA levels for TGF-beta1 and TGF-beta Type-II receptor and the histological characteristics of papillary thyroid carcinomas. The relative mRNA levels for TGF-beta1 and TGF-beta Type-II receptor did not show significant differences in thyroid carcinomas with or without lymph node metastases. There was a negative correlation between the TGF-beta Type-II receptor mRNA level and tumor size, while no significant correlation was observed between the TGF-beta1 mRNA level and tumor size. In conclusion, most papillary thyroid carcinomas overexpress TGF-beta1 mRNA but exhibit a reduction in TGF-beta Type-II receptor mRNA. The reduction of TGF-beta Type-II receptor mRNA may play a role in the pathogenesis of papillary thyroid carcinoma.

Adult↗

PubMed2006

Transforming growth factor beta1, bone connection.

Transforming Growth Factor beta1 (TGF beta1) exerts its functions both during embryogenesis, and in adult organism. TGF beta1 regulates cell proliferation, differentiation, motility and apoptosis. TGF beta1 is the most abundant growth factor in human bone. It is implicated in the pathogenesis of several bone diseases such as otosclerosis. During embryonic development, TGF beta1 plays a role in the migration of cells to the site of future skeletogenesis, the epithelial-mesenchymal interaction, and the formation of cellular condensations which dictates the general shape of the future skeletal elements. It also influences normal skeleton development by playing a critical role in inducing mesenchymal cell differentiation to either chondrocytes or osteoblasts. During Adult life, TGF beta1 has an influence on the maintenance of normal skeleton by playing a critical role on bone-forming cell namely, the osteoblast. TGF beta1 affects osteoblast differentiation, matrix formation, and mineralization. In MC3T3-E1 osteoblast-like cell line TGF beta1 inhibited the expression of the Runx2 and osteocalcin osteoblast differentiation markers. It interacts with many will known pathways in osteoblasts biology, such as Prostaglandin E2, Parathyroid hormone related peptide and Wnt-beta-catenin pathways. TGF beta1 exerts effects on osteocytes too. Treatment of pre-osteocytes with TGF alpha1 decreased cell death. Studied performed on osteoclast revealed that it inhibits both their proliferation and activity. This review briefly discusses the relation between this cytokine and the skeleton development and maintenance.

Animals↗

PubMed2003

Expression of transforming growth factor-beta1 and transforming growth factor-beta receptors in hepatocellular carcinoma and dysplastic nodules.

In this study we analyzed by immunohistochemistry the expression of TGF-beta1 protein and TGF-beta receptors I and II in 4 low-grade dysplastic nodules, 2 high-grade dysplastic nodules, 6 early, 22 small, and 62 advanced hepatocellular carcinomas. The expression of TGF-beta1 protein by hepatocytes was decreased in advanced hepatocellular carcinoma compared with small or early hepatocellular carcinoma(P < .05). Frequent and intense staining of TGF-beta1 protein was noted in the sinusoidal endothelium of advanced hepatocellular carcinomas despite of its decreased staining in hepatocellular carcinoma cells. Reduced expression of TGF-beta receptors I and II compared with surrounding nontumorous tissue were noted from the early hepatocellular carcinoma stage suggesting that down-regulation of TGF-beta receptors is correlated with progression from premalignant to malignant phenotype. Reduced expression of both TGF-beta1 and TGF-beta receptor II in neoplastic hepatocytes were also significantly correlated with increased tumor size and increased proliferative activity(P < .05). These findings suggest that during hepatocarcinogenesis, the inhibitory effects of TGF-beta1 protein on hepatocellular carcinoma cells is outweighed by its effects on stromal elements, which, overall, contributes indirectly to a tumor growth stimulatory environment. Also, the growth-inhibitory effects of TGF-beta1 may have been further negated by reduced TGF-beta receptors on hepatocellular carcinoma cells.

Carcinoma, Hepatocellular↗

PubMed2006

Enhancement of metastatic and invasive capacity of gastric cancer cells by transforming growth factor-beta1.

Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, exerts contradictory roles in different kinds of cells. A number of studies have revealed its involvement in the progression of many types of tumors. To investigate the effect of TGF-beta on gastric carcinoma, SGC7901, BGC823 and MKN28 (a TGF-beta-resistant cell line) adenocarcinoma clones were used. After pretreatment in serum-free medium with or without 10 ng/ml TGF-beta1, their experimental metastatic potential, chemotaxis, and invasive and adhesive ability were measured. Furthermore, zymography for gelatinase was processed. Liver colonies were also measured 4 weeks after inoculation of SGC7901, BGC823 and MKN28 in Balb/c nude mice, and an increase in the number of surface liver metastases was seen in SGC7901 (from 11.0+/-3.0 to 53.3+/-3.3) and BGC823 (from 9.3+/-2.5 to 60.0+/-2.8) groups, whereas there was no difference between MKN28 groups (from 35.2+/-3.8 to 38.5+/-2.7). In vitro experiments showed that TGF-beta1 increased the adhesion capacity of SGC7901 and BGC823 cells to immobilized reconstituted basement membrane/fibronectin matrices and promoted their penetration through reconstituted basement membrane barriers. Zymography demonstrated that enhanced invasive potential was partly due to the increased type IV collagenolytic (gelatinolytic) activity, but there was no difference in type IV collagenolytic activity and other biological behaviors between MKN28 groups. These results suggested that TGF-beta1 might modulate the metastatic potential of gastric cancer cells by promoting their ability to break down and penetrate basement membrane barriers and their adhesive and motile activities. We speculated that TGF-beta1 might act as a progression-enhancing factor in gastric cancer. Therefore blockage of TGF-beta or TGF-beta signaling might prevent gastric cancer cells from invading and metastasizing.

Animals↗

PubMed2004

The expression of matrix metalloproteinases-9, transforming growth factor-beta1 and transforming growth factor-beta receptor I in human atherosclerotic plaque and their relationship with plaque stability.

BACKGROUND: Transforming growth factor-beta (TGF-beta) and matrix metalloproteinases-9 (MMP-9) have been implicated in the pathogenesis of human atherosclerosis but their relationship during lesion progression are poorly understood. The objective of this study was to investigate the expression of MMP-9, TGF-beta1 and TGF-beta receptor I (TbetaR-I) in human atherosclerotic plaque and their relationship and plaque stability. METHODS: Specimens of human coronary artery atherosclerotic plaques were obtained from 41 patients undergoing coronary endarterectomy, and were paraffin embedded, sectioned at 4 microm intervals then stained with haematoxylin and eosin. They were divided into stable (with no or only little lipid core) and unstable plaque groups (with lipid core size > 40%): the immunohistochemical staining were performed for MMP-9, TGF-beta1 and TbetaR-I. RESULTS: The expression of MMP-9 in the unstable plaques was much higher than in the stable ones, but the expression of TGF-beta1 was higher in the stable plaques. There was no similar significant difference for TbetaR-I. Correlation analysis showed that there was a negative correlation between the expression of MMP-9 and TGF-beta1 (r = -0.332, P = 0.034 for average areal density; r = -0.373, P = 0.016 for average optical density). CONCLUSIONS: There were close relationships between MMP-9, TGF-beta1 and plaque stability. Enhanced production of MMP-9 may participate in the formation of unstable plaque, while TGF-beta1 maybe an important stabilizing factor in preventing transition into an unstable plaque phenotype.

Activin Receptors, Type I↗

PubMed1996

Formation of abdominal adhesions is inhibited by antibodies to transforming growth factor-beta1.

Transforming growth factor-beta (TGF-beta) is an important factor in regulating the inflammatory response and the production of extracellular matrix by fibroblasts. These two processes are linked in the formation of fibrous adhesions after abdominal surgery. When the mesothelium is injured a fibrin strand is produced which is populated first by inflammatory cells then by fibroblasts which secrete extracellular matrix forming a permanent adhesion. TGF-beta promotes both chemotaxis of monocytes and the production of extracellular matrix by fibroblasts. We have used a model of abdominal adhesions in rats in which a circle of peritoneum is dissected and then sutured into place again. After 2 weeks the rats are euthanized and the adhesions are scored. Six groups of 10 rats each underwent this surgery. Group I served as the operative control. Group II was treated with saline which was injected immediately after surgery and on Days 1 and 2 after surgery (vehicle control). Using the same protocol with saline as vehicle, the other four groups of rats were treated with nonspecific IgG (150 microgram per day), anti-TGF-beta (panspecific, 167 microgram per day), anti-TGF-beta1 (67 microgram per day), or anti-TGF-beta2 (50 microgram per day). The rats injected with anti-TGF-beta1 had significantly lower adhesion scores (P < 0.05) than the controls. Rats injected with anti-TGF-beta2 or anti-TGF-beta (panspecific) did not differ significantly from the control saline-injected rats. The results indicate that specifically reducing levels of TGF-beta1 alone can be effective in preventing abdominal adhesions.

Animals↗

PubMed2004

The effects of treatment with antibodies to transforming growth factor beta1 and beta2 following spinal cord damage in the adult rat.

We recently showed axonal ingrowth into fibronectin (FN) mats implanted into the spinal cord. However, little axonal growth was found from FN mats into intact spinal cord. Previous research has shown that this is due in part to astrocytosis around an area of CNS damage. Antibodies to transforming growth factor beta (TGFbeta) can diminish this astrocytosis. TGFbeta also has effects on macrophages and Schwann cells, both of which infiltrate the spinal cord following damage. We examined the axonal, Schwann cell, and macrophage infiltration into FN mats as well as the level of astrocytosis and chondroitin sulfate proteoglycan NG2 around FN implants incubated in TGFbeta antibodies and implanted into a lesion cavity in the spinal cord. We also examined the effects of applying TGFbeta antibodies to a spinal cord hemisection site. Anti-TGFbeta1 within FN mats resulted in extensive cavitation, with the area of damage being larger than the original lesion. Cavitation was also seen following application of anti-TGFbeta1 to a spinal cord hemisection site. No cavitation was seen following saline, non-immune IgG or anti-TGFbeta2 treatment. However, anti-TGFbeta2 treatment did result in diminished axonal growth and Schwann cell and macrophage infiltration. Around the implant site, anti-TGFbeta2 treatment resulted in a reduction in the level of astrocytosis but had not effect on levels of NG2. Similar effects were seen following anti-TGFbeta2 application to spinal cord hemisection sites. The results suggest that anti-TGFbeta1 exacerbates secondary damage by preventing the anti-inflammatory effect of endogenous TGFbeta1. Anti-TGFbeta2 did not enhance axonal regeneration in this model but did slightly reduce astrocytosis.

Animals↗

PubMed2001

Suppression of keratinocyte growth and differentiation by transforming growth factor beta1 involves multiple signaling pathways.

Transforming growth factor beta1 treatment of keratinocytes results in a suppression of differentiation, an induction of extracellular matrix production, and a suppression of growth. In this study we utilized markers specific for each of these functions to explore the signaling pathways involved in mediating these transforming-growth-factor-beta1-induced activities. In the first instance, we found that the induction of extracellular matrix production (characterized by 3TP-Lux reporter activity) was induced in both keratinocytes and a keratinocyte-derived carcinoma cell line, SCC25, in a dose-dependent manner. Furthermore, transforming growth factor beta1 also suppressed the differentiation-specific marker gene, transglutaminase type 1, in both keratinocytes and SCC25 cells. In contrast, transforming growth factor beta1 inhibited proliferation of keratinocytes but did not cause growth inhibition in the SCC25 cells. Transforming-growth-factor-beta1-induced growth inhibition of keratinocytes was characterized by decreases in DNA synthesis, accumulation of hypophosphorylated Rb, and the inhibition of the E2F:Rb-responsive promoter, cdc2, and an induction of the p21 promoter. When the negative regulator of transforming growth factor beta1 signaling, SMAD7, was overexpressed in keratinocytes it could prevent transforming-growth-factor-beta1-induced activation of the 3TP-Lux and the p21 promoter. SMAD7 could also prevent the suppression of the transglutaminase type 1 by transforming growth factor beta1 but it could not inhibit the repression of the cdc2 promoter. These data indicate that the induction of 3TP-Lux and p21 and the suppression of transglutaminase type 1 are mediated by a different proximate signaling pathway to that regulating the suppression of the cdc2 gene. Combined, these data indicate that the regulation of transforming growth factor beta1 actions are complex and involve multiple signaling pathways.

Cell Differentiation↗

PubMed2005

Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1.

BACKGROUND AND AIMS: Transforming growth factor beta1 (TGF-beta1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC) might also be subject to immunoregulation by TGF-beta1. METHODS: MC were isolated from the intestinal mucosa, purified, and cultured in vitro in the presence of stem cell factor (SCF) with or without TGF-beta1. Growth characteristics, phenotype, and immunological mediator release of MC were analysed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, western blot, and different immunoassays, respectively. RESULTS: TGF-beta1 dose dependently (ED50 approximately = 0.1 ng/ml) inhibited SCF dependent growth of human intestinal MC by both enhancing apoptosis and decreasing proliferation. In parallel, TGF-beta1 increased the percentage of connective tissue-type MC expressing tryptase and chymase while downregulating expression of the receptors for IgE and SCF. Furthermore, TGF-beta1 dramatically changed the profile of mediators released by MC following IgE receptor crosslinking. Release of histamine, cysteinyl-leukotrienes, and tumour necrosis factor alpha was strongly reduced whereas prostaglandin D2 generation and cyclooxygenase 1 and 2 expression were upregulated by TGF-beta1. CONCLUSIONS: Our data indicate that TGF-beta1 acts as a novel potent inhibitor and modulator of human intestinal MC effector functions. The change in MC mediator release profile and protease expression induced by TGF-beta1 might be of relevance for the control of MC associated disorders of the intestine such as allergic reactions, Crohn's disease, irritable bowel syndrome, and parasitic infection.

Apoptosis↗

PubMed2000

DNA-liposome versus adenoviral mediated gene transfer of transforming growth factor beta1 in vascularized cardiac allografts: differential sensitivity of CD4+ and CD8+ T cells to transforming growth factor beta1.

We have developed a model of transforming growth factor (TGF)beta1 gene transfer into mouse vascularized cardiac allografts to study the use of gene transfer as an immunosuppressive therapy in transplantation. Donor hearts were perfused with either DNA-liposome complexes or adenoviral vectors that encode the active form of human TGFbeta1. DNA-liposome mediated transfection prolonged allograft survival in approximately two-thirds of transplant recipients, while adenoviral delivery of TGFbeta1 was not protective. Protective TGFbeta1 gene transfer was associated with reduced Th1 responses and an inhibition of the alloantibody isotype switch. The protective effects of TGFbeta1 gene transfer were overridden by exogenous interleukin-12 administration. Interestingly, alloreactive CD4+ and CD8+ cells exhibited distinct sensitivities to TGFbeta1 gene transfer: CD4+ Th1 function was abrogated by this modality, although CD8+ Th1 function was not. Transient depletion of recipient CD8+ cells markedly prolonged the survival of grafts transfected with either DNA-liposome complexes or adenoviral vectors. Transgene expression persisted for at least 60 days, and Th1 responses were not detectable until CD8+ T cells repopulated the periphery. However, long-term transfected allografts appeared to exhibit exacerbated fibrosis and neointimal development. These manifestations of chronic rejection were absent in long-term transfected isografts, suggesting that long-term expression of active TGFbeta1 alone is not sufficient to induce fibrosis of the grafts. Collectively, these data illustrate the utility of immunosuppressive gene therapy as a treatment for transplantation when combined with additional conditioning regimens. Further, they illustrate that alloreactive CD4+ and CD8+ cells may be differentially influenced by cytokine manipulation strategies.

Adenoviridae↗

PubMed2002

Latent and active transforming growth factor beta1 released from genetically modified keratinocytes modulates extracellular matrix expression by dermal fibroblasts in a coculture system.

Transforming growth factor beta1 is a multifunctional cytokine involved in many aspects of wound healing. Here we report the effects of both latent and active transforming growth factor beta1 released from genetically modified keratinocytes on extracellular matrix expression by dermal fibroblasts in a coculture system. Human keratinocytes were genetically modified with adenovirus containing cDNA for latent transforming growth factor beta1 (AdTGF-beta1) or active transforming growth factor beta1 (AdTGF-beta1(223/225)) or LacZ and cultured with human dermal fibroblasts. Northern blotting for mRNA confirmed that keratinocytes were successfully transduced with the adenoviruses as the cDNA transcripts are smaller than native transforming growth factor beta1 mRNA. An enzyme-linked immunosorbent assay specific for transforming growth factor beta1 demonstrated that the transforming growth factor beta1 produced by the genetically modified keratinocytes was able to pass through the membrane separating the two cell layers. Levels of transforming growth factor beta1 were significantly higher for both latent (p < 0.0001) and active (p < 0.0001) transforming growth factor beta1 compared to the LacZ control. Without acid activation of samples, keratinocytes transduced with the active transforming growth factor beta1 construct exhibited significantly higher levels of transforming growth factor beta1 than either the latent construct or the LacZ control (p < 0.0001). The transforming growth factor beta1 produced was biologically active, as shown by the plasminogen activator inhibitor assay (p < 0.0001). To demonstrate that transforming growth factor beta1 had an effect on underlying fibroblasts, mRNA was extracted and analyzed using Northern analysis. Latent transforming growth factor beta1 significantly increased the expression of type I collagen mRNA (p < 0.05) but did not significantly affect collagenase mRNA. Active transforming growth factor beta1 significantly increased type I collagen mRNA (p < 0.005) while also decreasing collagenase mRNA (p < 0.05). These results illustrate the ability of increased levels of transforming growth factor beta1 to override the effects of normal keratinocytes on the behavior of dermal fibroblasts.

Adenoviridae↗

PubMed2001

Effect of ulcerative colitis activity on plasma concentration of transforming growth factor beta1.

Enhanced expression of transforming growth factor-beta1 (TGF-beta1) demonstrated in human colonic mucosa of patients with ulcerative colitis (UC), indicates its possible significance in the pathogenesis of this disease. The aim of this study was to evaluate plasma TGF-beta1 concentration in patients with different degrees of colonic mucosal injury, as a possible indicator of ulcerative colitis activity. TGF-beta1 concentration was measured with an enzyme immunoassay (EIA) in plasma of 45 patients with endoscopically confirmed UC. Values observed in UC patients (40.5+/-15.9 ng/ml) were significantly higher than in healthy people (18.3+/-11.6 ng/ml) and higher than in patients with irritable colon syndrome (ICS), (20.5+/-13.6 ng/ml). The highest plasma TGF-beta1 (58.6+/-112.1 ng/ml) was in patients with the severe UC course. TGF-beta1 level analysed in all UC patients revealed significant positive correlation with scored degree of mucosal injury (r=0.396;P<0.01). Among other possible laboratory markers of the disease activity, only C-reactive protein concentration demonstrated significant correlation. Enhanced production of TGF-beta1 can be related to inflammation activity. Measurement of plasma TGF-beta1 may be considered as a biomarker of the disease activity.

Adult↗

PubMed2006

Accurate measurement and clinical significance of urinary transforming growth factor-beta1.

Transforming growth factorbeta1 (TGF-beta1) is the main modulator of the healing process after tissue injury. In the kidney, if TGF-beta1 release is not switched off, extracellular matrix components (ECM) are accumulated and tissue fibrosis occurs. Urinary TGF-beta1 levels reflect its renal production and it has been determined in various types of glomerular disease. In this review, a critical analysis of the different immunoassays that have been used for the measurement of TGF-beta1 in the urine is presented and the importance of the serial determination of urinary TGF-beta1 levels in patients with various types of renal disease is discussed.

Enzyme-Linked Immunosorbent Assay↗

PubMed2001

Genetic variation in the transforming growth factor beta1 gene in multiple sclerosis.

Transforming growth factor beta1 (TGFbeta1) is a Th2 cytokine encoded on chromosome 19q13, a region possibly linked to multiple sclerosis (MS). TGFbeta1 exerts favorable effects on experimental allergic encephalomyelitis. We performed a comprehensive search for genetic variants in this gene in 122 population-based sporadic cases of MS. We detected six variants, including three missense variants. We tested for association of the variants with susceptibility and course of MS and for linkage and transmission disequilibrium in a family series consisting of 395 samples in 59 pedigrees. Genetic variation in TGFB1 does not appear to contribute in a major way to susceptibility to MS.

Adult↗

PubMed2001

Decreased levels of precursor transforming growth factor beta1 in human colorectal cancer.

Transforming growth factor (TGF) beta1 is a growth factor with wide-ranging effects on proliferation, differentiation, immunosuppression, apoptosis and matrix remodelling. TGFbeta1 seems to have an antitumorigenic role in the gastrointestinal tract but may also be associated with the development of colorectal cancer. Initially, TGFbeta1 is produced in a latent (precursor) form in epithelial cells and then is activated by a not clearly understood multistep process. In this study, we analysed precursor TGFbeta1 protein expression (n=40) and TGFbeta1 gene expression (n=49) in human colorectal adenocarcinomas and 49 normal adjacent tissue. Out of these 49 normal tissues 40 were matched. Western blot analysis revealed that the precursor TGFbeta1 protein levels were generally lower in colorectal cancerous tissue compared to adjacent non-cancerous tissue (P<0.001). Furthermore, with real-time PCR our results cannot reflect a statistically significant difference in TGFbeta1 gene expression between the tumour tissue and normal tissue. These finds indicate that it is likely that there are mechanisms which control precursor TGFbeta1 protein expression by factor(s) at the level of pre-translation of the TGFbeta1 transcript and/or at the level of post-translation of the TGFbeta1 protein in the tumours. This process may be related to carcinogenesis and poses the question whether the suppression of the precursor TGFbeta1 is an early event, in vivo, in the human colorectal adenoma-carcinoma sequence.

Adenoma↗