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C Bernabeu

Publications and source records attributed to C Bernabeu.

At least 19 recordsLinked to original sources
PubMed2005

Temporal changes in renal endoglin and TGF-beta1 expression following ureteral obstruction in rats.

Chronic renal disease is characterized by the accumulation of extracellular matrix proteins in the kidney and a loss of renal function. Tubulointerstitial fibrosis has been reported to play an important role in the progression of chronic renal diseases. Transforming growth factor-beta1 (TGF-beta1) is a profibrotic cytokine playing a major contribution to fibrotic kidney disease. Endoglin is a membrane glycoprotein of the TGF-beta1 receptor system. The aim of this work was to determine the time-course expression of renal type I and IV collagens, endoglin and TGF-beta1 in a rat model of induced tubulointerstitial fibrosis at 1, 3, 10 and 17 days after unilateral ureteral obstruction (UUO). In 17 days-ligated (L)-renal samples, a marked interstitial fibrosis was detected by Masson's trichromic and Sirius red staining, accompanied by an increase in type I collagen expression as shown by immunohistochemical analysis. Northern blot studies revealed a progressive increase in collagen alpha2(I), TGF-beta1 and endoglin mRNA expression in L kidneys when compared with the corresponding non-ligated (NL) kidneys from the animals subjected to left UUO. Seventeen days after UUO, significant increases in collagen alpha2(I), collagen alpha1(IV), TGF-beta1 and endoglin mRNA levels were detected in L kidneys vs NL kidneys. Significantly higher levels of the protein endoglin were found in L kidneys than in NL kidneys 10 and 17 days following obstruction. A marked increase expression for endoglin and TGF-beta1 was localized in renal interstitium by immunohistochemical studies 17 days after obstruction. In conclusion, this work reports the upregulation of endoglin coincident to that of its ligand TGF-beta1 in the kidneys of rats with progressive tubulointerstitial fibrosis induced by UUO.

Animals↗
PubMed2002

Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts.

OBJECTIVE: As an initial approach to understanding the basis of the systemic sclerosis (SSc; scleroderma) phenotype, we sought to identify genes in the transforming growth factor beta (TGF beta) signaling pathway that are up-regulated in lesional SSc fibroblasts relative to their normal counterparts. METHODS: We used gene chip, differential display, fluorescence-activated cell sorter, and overexpression analyses to assess the potential role of TGF beta signaling components in fibrosis. Fibroblasts were obtained by punch biopsy from patients with diffuse cutaneous SSc of 2-14 months' duration (mean 8 months) and from age- and sex-matched healthy control subjects. RESULTS: Unexpectedly, we found that fibroblasts from SSc patients showed elevated expression of the endothelial cell-enriched TGF beta receptor endoglin. Endoglin is a member of the nonsignaling high-affinity TGF beta receptor type III family. The expression of endoglin increased with progression of disease. Transfection of endoglin in fibroblasts suppressed the TGF beta-mediated induction of connective tissue growth factor promoter activity. CONCLUSION: SSc is characterized by overproduction of matrix; that is, genes that are targets of TGF beta signaling in normal fibroblasts. Our findings suggest that lesional SSc fibroblasts may overexpress endoglin as a negative feedback mechanism in an attempt to block further induction of profibrotic genes by TGF beta.

Antigens, CD↗
PubMed2001

Angiogenesis in breast cancer: the role of transforming growth factor beta and CD105.

The progression of breast cancer depends on the establishment of a neovasculature, by a process called angiogenesis. Angiogenesis is an invasive cellular event that requires the co-ordination of numerous molecules including growth factors and their receptors, extracellular proteins, adhesion molecules, and proteolytic enzymes. TGFbeta has emerged to be a major modulator of angiogenesis by regulating endothelial cell proliferation, migration, extracellular matrix (ECM) metabolism, and the expression of adhesion molecules. It is a potent growth inhibitor of normal mammary epithelial cells and a number of breast cancer cell lines. It seems that TGFbeta exerts pleiotropic effects in the oncogenesis of breast cancers in a contextual manner, i.e., it suppresses tumourigenesis at an early stage by direct inhibition of angiogenesis and tumour cell growth. However, over-production of TGFbeta by an advanced tumour may accelerate disease progression through indirect stimulation of angiogenesis and immune suppression. The cell membrane antigen CD105 (endoglin) binds TGFbeta1 and TGFbeta3 and is preferentially expressed in angiogenic vascular endothelial cells. The reduction of CD105 levels in HUVEC leads to in vitro angiogenesis inhibition and massive cell mortality in the presence of TGFbeta1. CD105 null mice die in utero with impaired vasculature, indicating the pivotal role of CD105 in vascular development. The administration of an immunotoxin-conjugate, mab to CD105, induces long-term and complete regression of breast cancer growth in SCID mice. Therefore, CD105 is a promising vascular target for antiangiogenic therapy.

Animals↗
PubMed2001

Up-regulation of endoglin, a TGF-beta-binding protein, in rats with experimental renal fibrosis induced by renal mass reduction.

BACKGROUND: The central process in chronic renal failure is the progressive accumulation of extracellular matrix in the glomeruli and in the tubulo-interstitial space, resulting in renal fibrosis. Transforming growth factor-beta1 (TGF-beta1) up-regulation plays a major role in the genesis of renal fibrosis. Endoglin is a membrane glycoprotein that binds TGF-beta1 and TGF-beta3 with high affinity. An increased level of endoglin immunostaining has been demonstrated previously in biopsies from patients with chronic progressive renal disease. We have assessed the expression of endoglin in the rat 5/6th renal mass reduction (RMR) model. METHODS: One, 3 and 5 months after RMR, mean arterial pressure and renal function were measured, animals were sacrificed, renal fibrosis was evaluated quantitatively and the expression of endoglin was assessed by western blot, northern blot and immunohistochemistry. RESULTS: RMR induced a progressive increase in mean arterial pressure and urinary protein excretion. Renal corpuscular area, and mesangial and interstitial fibrosis increased with time after RMR. Immunohistochemical staining for endoglin demonstrated its expression mainly on the endothelial surface of major vessels. In kidneys 1 and 3 months after RMR, the expression of endoglin in renal corpuscles was limited to Bowman's parietal epithelium. In rats 5 months after RMR, the immunoexpression in glomerular endothelium was more marked. Northern blot analysis revealed that rats with RMR showed an increase in the expression of mRNA for endoglin, only at 5 months after RMR. Western blot analysis gave a different time course: a marked increase in the first month, a decrease in the 3rd month and a further increase in the 5th month after RMR. CONCLUSIONS: The present study demonstrates increased endoglin expression in rats with severe hypertension and renal damage. This increased endoglin expression coincides with the period of higher renal damage and renal dysfunction.

Animals↗
PubMed2000

Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2.

ALK-1 (activin receptor-like kinase-1), a type I receptor of the transforming growth factor (TGF)-beta superfamily, is the gene mutated in hereditary hemorrhagic telangiectasia type 2 (HHT2) while endoglin is mutated in HHT1. Using a novel polyclonal antibody to ALK-1, we measured ALK-1 expression on human umbilical vein endothelial cells (HUVEC) of newborns from HHT families whose affected members had normal endoglin levels. ALK-1 levels were specifically reduced in three HUVEC with ALK-1 missense mutant codons, and normal in two newborns not carrying the missense mutations present in the clinically affected relatives. Levels were also normal in a HUVEC with deletion of S232 in the ATP binding site of ALK-1. Thus HHT2 appears to be associated with a loss of function of the mutant allele due to a reduction in either protein level or activity. We also report three new ALK-1 missense mutations leading to G48E/A49P, C344Y and E407D substitutions. In COS-1 transfected cells, ALK-1 was found in the TGF-beta1 and -beta3 receptor complexes in association with endoglin and TbetaRII, but not in activin receptor complexes containing endoglin. In HUVEC, ALK-1 was not detectable in the TGF-beta1 or -beta3 receptor complexes. However, in the absence of ligand, ALK-1 and endoglin interactions were observed by immunoprecipitation/western blot in HUVEC from normal as well as HHT1 and HHT2 patients. Our data suggest a transient association between these two proteins of the TGF-beta superfamily, both required at a critical level to ensure vessel wall integrity.

Activin Receptors↗
PubMed2000

Endoglin, a TGF-beta receptor-associated protein, is expressed by smooth muscle cells in human atherosclerotic plaques.

Endoglin is a transmembrane protein that is found in association with transforming growth factor-beta (TGF-beta) superfamily receptor complexes and has an expression pattern that appears to be restricted primarily to endothelial cells, activated macrophages, trophoblasts, and fibroblasts. Since mutations in endoglin have been shown to be linked to hereditary hemorrhagic telangiectasia type 1, a disease manifested as vascular malformations characterized by excessive layers of vascular smooth muscle cells (VSMC), the expression of endoglin was investigated in VSMC. In vivo, the majority of SMC in human atherosclerotic plaques expressed high levels of endoglin, while endoglin was not detected in SMC from samples of the normal arterial wall. In vitro studies demonstrate that human aortic smooth muscle cells (HASMC) express the L-isoform of endoglin. Like endothelial cells, HASMC express endoglin protein as a dimer on the cell surface that binds TGF-beta1. In vitro, endoglin expression by HASMC is upregulated in response to TGF-beta1, suggesting that the presence of this factor in the atherosclerotic plaque might be responsible for the increased expression of endoglin. The demonstration of increased levels of endoglin in VSMC in human atherosclerotic plaques suggests a role for SMC endoglin in the maintenance of vascular integrity and in the response of the vessel wall to injury.

Antigens, CD↗
PubMed2000

CD105 antagonizes the inhibitory signaling of transforming growth factor beta1 on human vascular endothelial cells.

CD105 (endoglin), a receptor for transforming growth factor beta (TGFbeta), is highly expressed in tissue-cultured, activated endothelial cells in vitro and in tissues undergoing angiogenesis in vivo. The absence of CD105 in knockout mice leads to their death from defective vascular development, but the role of CD105 in the modulation of angiogenesis has not been elucidated. TGFbeta1 is a well-recognized regulator of angiogenesis. Using an antisense approach, we have shown that inhibition of CD105 protein translation in cultured human endothelial cells enhances the ability of TGFbeta1 to suppress growth and migration in these cells. The ability of endothelial cells to form capillary tubes was evaluated by the use of a 3-dimensional collagen matrix system where TGFbeta1 not only reduced the length of capillary-like structures, but also caused massive mortality in CD105-deficient cells compared to control cultures. These results provide direct evidence that CD105 antagonizes the inhibitory effects of TGFbeta1 on human vascular endothelial cells and that normal cellular levels of CD105 are required for the formation of new blood vessels.

Animals↗
PubMed1998

Role of endoglin in cellular responses to transforming growth factor-beta. A comparative study with betaglycan.

Endoglin (CD105) is the target gene for the hereditary hemorrhagic telangiectasia type I (HHT1), a dominantly inherited vascular disorder. It shares with betaglycan a limited amino acid sequence homology and being components of the membrane transforming growth factor-beta (TGF-beta) receptor complex. Using rat myoblasts as a model system, we found that overexpression of endoglin led to a decreased TGF-beta response to cellular growth inhibition and plasminogen activator inhibitor-1 synthesis, whereas overexpression of betaglycan resulted in an enhanced response to inhibition of cellular proliferation and plasminogen activator inhibitor-1 induced expression in the presence of TGF-beta. The regulation by endoglin of TGF-beta responses seems to reside on the extracellular domain, as evidenced by the functional analysis of two chimeric proteins containing different combinations of endoglin and betaglycan domains. Binding followed by cross-linking with 125I-TGF-beta1 demonstrated that betaglycan expressing cells displayed a clear increase (about 3. 5-fold), whereas endoglin expressing cells only displayed an slight increment (about 1.6-fold) in ligand binding with respect to mock transfectants. SDS-polyacrylamide gel electrophoresis analysis of radiolabeled receptors demonstrated that expression of endoglin or betaglycan is associated with an increased TGF-beta binding to the signaling receptor complex; however, while endoglin increased binding to types I and II receptors, betaglycan increased the binding to the type II receptor. Conversely, we found that TGF-beta binding to endoglin required the presence of receptor type II as evidenced by transient transfections experiments in COS cells. These findings suggest a role for endoglin in TGF-beta responses distinct from that of betaglycan.

Animals↗
PubMed1998

Immunodetection and characterisation of soluble CD105-TGFbeta complexes.

CD105 (endoglin) is a receptor for transforming growth factor beta (TGFbeta). Although methods to measure soluble forms of TGFbeta and CD105 have been published, no assay is available to quantify the receptor-ligand complexes. We describe both an indirect enzyme-linked immunosorbent assay for the quantitation of soluble CD105-TGFbeta1 and the characterization of the complexes by immunoprecipitation and immunoblotting. Mab E9, specifically reactive with CD105, was utilised as the capture reagent in the ELISA system. Detection of complexes was achieved using chicken antibody against TGFbeta1 and the subsequent detection of bound antibody demonstrated by the addition of anti-species antiserum conjugated to horseradish peroxidase (HRP). By using enhanced chemiluminescence and optimised antibodies, the assay was made sufficiently sensitive and reproducible to detect low levels of circulating complexes. Whether the assay had any practical applications was evaluated in breast cancer patients. Plasma levels of CD105-TGFbeta1 were significantly elevated in 59 patients with breast cancer compared to 52 age matched normal women (p < 0.001). Immunoprecipitation using a rabbit anti-CD105 antibody, which reacts with both dimeric and monomeric CD105, and immunoblotting showed that three molecular forms of CD105-TGFbeta1 complexes > 200, 195, and 125 kDa existed in the plasma. We believe these represent the oligomer, dimer and probably the protease degraded form of CD105 complexed to TGFbeta1. The resistance to hypertonic solution, SDS and heat treatment suggested that the soluble CD105-TGFbeta1 complex may be linked by covalent bonds. The measurement of CD105-TGFbeta complexes in the circulation may have important clinical applications not only in cancer but also in patients with other angiogenic diseases such as rheumatoid arthritis, myocardial infarction and stroke.

Antigens, CD↗
PubMed1997

The use of recombinant vaccinia virus to generate monoclonal antibodies against the cell-surface glycoprotein endoglin.

Characterization of novel cell-surface protein molecules, initially identified by cDNA cloning techniques, usually requires the generation of specific antibodies to further analyze their biochemical and/or functional properties. Here we report a simple method, using recombinant vaccinia virus, for the generation of monoclonal antibodies (mAb) to the cell-surface antigen endoglin. A recombinant vaccinia virus carrying a cDNA encoding human endoglin was inserted into the thymidine kinase locus under the control of the 7.5k vaccinia virus promoter. Infection of Balb/c mice with this recombinant virus led to the generation of specific polyclonal antibodies, as demonstrated by the antisera reactivity against human endoglin transfectants. The spleen cells of these infected animals were fused to myeloma cells, allowing efficient generation of several hybridomas which secrete mAbs to human endoglin, as evidenced by their reactivity with purified endoglin as well as with endoglin transfectants. Some of the mAbs selected seem to be specific for regions of endoglin conserved among different species as evidenced by their cross-reactivity with chicken endoglin. These results underline the utility of recombinant vaccinia virus to generate antibodies with novel properties to new cell surface proteins such as endoglin.

Animals↗
PubMed1996

Characterization of TGF-beta 1-binding proteins in human bone marrow stromal cells.

The proliferation and differentiation of haemopoietic progenitor cells is dependent on their close relation with bone marrow stromal cells, which constitute a source of cytokines as well as expressing receptors for both the cytokines and progenitor cell adhesion molecules necessary for regulated haemopoiesis. We have generated human bone marrow stromal cell cultures and analysed the TGF-beta 1 receptor components expressed by these cells. [125I]TGF-beta 1-affinity labelling experiments showed the involvement of type I and II receptors in the binding of TGF-beta 1, as demonstrated by specific immunoprecipitation of [125I]TGF-beta 1-receptor complexes. In addition, large TGF-beta 1-labelled complexes displaying an electrophoretic mobility similar to betaglycan were also observed in these experiments. Endoglin, another component of the TGF-beta receptor system, was detected by flow cytometry on the surface of cultured marrow stromal cells, and in the human bone marrow stromal cell line Str-5, and was immunoprecipitated from surface-iodinated cells. Endoglin on the stromal cells was able to bind TGF-beta 1, as demonstrated by specific immunoprecipitation of [125I]TGF-beta 1-endoglin complexes using anti-endoglin antibodies. The results presented provide evidence that bone marrow stromal cells are fully capable of responding to TGF-beta 1. Given the important role of TGF-beta as a regulator of the synthesis of cytokines and cytokine receptors, as well as cell adhesion molecules, these data indicate that the binding of TGF-beta 1 by stromal cells might represent an important step in the regulation of the proliferation and differentiation of haemopoietic progenitor cells.

Antigens, CD↗
PubMed1995

[Evaluation of the nutritional status of a rural child population in a Valencia community: the Pego study].

OBJECTIVE: To evaluate the nutritional state of the child population of Pego (Alicante) in order to define the patterns of normality and check the validity of the anthropometric parameters most commonly used in evaluating nutritional status. DESIGN: A descriptive crossover study. SETTING: Valls de Pego Primary Care Health Centre. PATIENTS: 943 healthy children and adolescents aged 0 to 17 were studied out of a target population of 2,150 who were seen for treatment at the Health Centre for reasons which had nothing to do with nutritional problems. INTERVENTIONS: Between july 1989 and december 1990, a simple anthropometric assessment of each patient was carried out: obtaining weight, height, the nutrition or Shukla index and the Quetelet index. MAIN RESULTS: Nutritional distribution was clearly displaced towards high values on the nutritional scale, with 14% obesity and 15% overweight as against 13% at risk of malnutrition. There was more overweight and obesity at a higher age and in males. CONCLUSIONS: This prevalence of nutritional disturbances is similar to that in other Spanish studies and confirms both the size of the problem of obesity in the prevention of related pathologies in adults and the relevance of the adult's Nutritional History throughout his/her life. The study made clear the good correlation and utility of the Shukla and Quetelet indexes.

Adolescent↗
PubMed1994

Regulated expression of p150,95 (CD11c/CD18; alpha X/beta 2) and VLA-4 (CD49d/CD29; alpha 4/beta 1) integrins during myeloid cell differentiation.

Integrins are a family of cell surface heterodimers which mediate both cell-cell and cell-extracellular matrix interactions and affect cellular differentiation through their signal transduction capacity. Integrin expression is regulated during differentiation as well as by numerous growth factors and cytokines. We have analyzed the changes in p150,95 (CD11c/CD18 or alpha X/beta 2) and VLA-4 (CD49d/CD29 or alpha 4/beta 1) integrin subunits mRNA levels that take place during the myeloid differentiation of HL60 and U937 cells, and compared them to other integrins with similar functional activities. Northern blot analysis revealed that the monocytic differentiation of U937 and HL60 cells alters the alpha X and alpha 4 mRNA steady-state levels: alpha X mRNA is induced de novo whereas alpha 4 mRNA decreases to undetectable levels. Both changes were dependent on the activity of protein kinase C and were also observed upon granulocytic differentiation of HL60 cells. Parallel analysis of other integrin subunits mRNA (beta 1, alpha 5, beta 7) demonstrated that the mRNA levels for the alpha subunits of the fibronectin receptors alpha 4/beta 1 (VLA-4) and alpha 5/beta 1 (VLA-5) are differentially regulated during the monocytic differentiation of myeloid cell lines, and suggested that myeloid cells express a heterodimer formed by the association of beta 7 with an integrin alpha subunit distinct from alpha 4. Nuclear transcription assays and functional analysis of the alpha X and alpha 4 promoter regions demonstrated that the transcription rate of the alpha X gene is considerably elevated after phorbol 12-myristate 13-acetate treatment of U937 cells, while that of alpha 4 is almost unaffected, suggesting that post-transcriptional mechanisms are causing the extremely low alpha 4 mRNA levels observed in differentiated U937 cells.

Blotting, Northern↗
PubMed1993

Structural and functional studies on the interaction of sodium dodecyl sulfate with beta-galactosidase.

The effect of sodium dodecyl sulfate (SDS) on enzyme activity, electrophoretic behavior, and conformation of Escherichia coli beta-galactosidase is presented. Fourier-transform infrared spectroscopy (FT-IR), previously used to study the structure of native beta-galactosidase has been applied to examine the detergent effects on the enzyme. At 20 degrees C, the presence of 1% SDS does not cause appreciable changes in the secondary structure, and enzyme activity is preserved; however, 10% SDS produces complete enzyme inactivation and FT-IR spectroscopy indicates a concomitant change in conformation. Thermal denaturation of beta-galactosidase starts at approximately 53 degrees C in the absence and at approximately 46 degrees C in the presence of 1% SDS, indicating tertiary structure changes; also, a good correlation between structural (FT-IR) and functional (Arrhenius plots) data is observed. The secondary structure of thermally denatured beta-galactosidase contains mainly extended structures, and intermolecular interactions produce protein aggregation. In the presence of 10% SDS, however, the hydrophobic segments of the protein are stabilized by SDS into helical structures without protein aggregation. At 30 degrees C, in the presence of 1% SDS, two protein bands are resolved by gel electrophoresis, only one of them being active. A model for SDS-galactosidase interaction is proposed, according to which, at low surfactant concentrations, SDS molecules bind the outer surface of the protein, without affecting the protein core. Higher detergent concentrations produce a larger conformational change involving enzyme inactivation and increased accessibility of the solvent to the protein core. Increasing temperature in the presence of 10% SDS leads to a facilitated access of surfactant molecules to the inner protein regions and to an increase of the beta-galactosidase alpha-helical content.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

Inhibition of T-cell proliferation by rat synoviocytes.

Antigen presentation by synoviocytes to arthritis-related T-cell clones was studied in Lewis rats. Freshly isolated synoviocytes may be able to take up and process mycobacterial antigens but they seem inefficient as antigen presenting cells. Furthermore, synovial cells inhibited the specific proliferative responses of T lymphocytes by a mechanism which apparently was not antigen-specific or mediated by secreted cytokines. Synovial cells isolated from rats at the period of developing adjuvant arthritis showed a lower inhibitory capacity associated with a lower degree of antigen clearance. These results suggest that synoviocytes might inhibit T-cell responses in normal joints and that this negative control diminishes following arthritis induction.

Animals↗
PubMed1993

Modulation of adjuvant arthritis in Lewis rats by recombinant vaccinia virus expressing the human 60-kilodalton heat shock protein.

The immune response to the mycobacterial 65-kDa heat shock protein (hsp65) is considered an important event in the induction of adjuvant arthritis (AA) in rats; this induction probably occurs through a molecular mimicry mechanism involving cross-reactivity against the rat homolog hsp60. To analyze the role of mammalian molecule hsp60 in arthritis, we generated a recombinant vaccinia virus (hsp60-VV) carrying the human hsp60 gene inserted into the thymidine kinase locus under the control of the 7.5k vaccinia virus promoter. Human hsp60 is almost identical to its rat homolog (97.4% linear amino acid homology) and shares about 50% of amino acid positions with Mycobacterium tuberculosis hsp65. The latter supposedly carries a critical epitope for AA induction that is not present in human hsp60. Infections with hsp60-VV of monkey cell cultures led to the expression of the human hsp60 molecule, as evidenced by immunoblotting analysis with specific monoclonal antibodies. Also, Lewis rats infected with hsp60-VV produced specific antibodies, demonstrating the in vivo expression of human hsp60 in the infected animals. Therefore, we used hsp60-VV to analyze whether the delivery of hsp60 could affect the induction of AA in Lewis rats. hsp60-VV clearly reduced and retarded arthritic symptoms when administered to rats at day 7 after AA induction. In contrast, inoculation of rats with a control recombinant vaccinia virus did not affect the course of the disease. The improvement in AA with hsp60-VV administration was associated with a specific immune response, as determined by the presence of antibodies to hsp60 in the sera and the proliferation induced by hsp60 of T cells from popliteal lymph nodes. These results support a critical role for immunity to heat shock proteins in AA. Since the protective construct is virtually identical to rat homolog hsp60, we conclude that immunity directed to conserved areas of this family of proteins is directly involved in the pathogenesis of AA.

Animals↗
PubMed1992

Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells.

Endoglin, a dimeric membrane glycoprotein expressed at high levels on human vascular endothelial cells, shares regions of sequence identity with betaglycan, a major binding protein for transforming growth factor-beta (TGF-beta) that co-exists with TGF-beta receptors I and II in a variety of cell lines but is low or absent in endothelial cells. We have examined whether endoglin also binds TGF-beta and demonstrate here that the major TGF-beta 1-binding protein co-existing with TGF-beta receptors I and II on human umbilical vein endothelial cells is endoglin, as determined by specific immunoprecipitation of endoglin affinity-labeled with 125I-TGF-beta. Furthermore, endoglin ectopically expressed in COS cells binds TGF-beta 1. Competition affinity-labeling experiments showed that endoglin binds TGF-beta 1 (KD approximately 50 pM) and TGF-beta 3 with high affinity but fails to bind TGF-beta 2. This difference in affinity of endoglin for the TGF-beta isoforms is in contrast to beta-glycan which recognizes all three isoforms. TGF-beta however is binding with high affinity to only a small fraction of the available endoglin molecules, suggesting that some rate-limiting event is required to sustain TGF-beta binding to endoglin.

Antigens, CD↗