UNIPROT:P56851 - FACTA Search

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Query: UNIPROT:P56851 (epididymal)
11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vascular cell responses to the type 1, 2, and 3 isoforms of transforming growth factor-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMC3) as well as rat epididymal fat pad microvascular endothelia (RFCs). Three distinct bioassays indicated that TGF-beta elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. These assays are: inhibition of proliferation, cell migration, and neovascularization. By contrast the cellular responses to TGF-beta 1 and TGF-beta 3 differed from those to TGF-beta 2. Three distinct receptor assays revealed the presence of type I and type II TGF-beta 1 cell surface binding proteins on BAECs, BASMCs, and RFCs. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF-beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent on the cell type examined. The ratios of type I to type II TGF-beta receptors in these three vascular cell types vary from 1:1 in BAECs to 1.5:1 in RFCs to 3:1 in BASMCs and can be correlated with the differences noted in cellular responses to TGF-beta 1 and TGF-beta 2 in proliferation, migration, and in vitro angiogenic assays.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of vascular cell behavior by transforming growth factors beta. 163 50

Transforming growth factor-beta 1 (TGF-beta 1) is angiogenic in vivo. In two-dimensional (2-D) culture systems microvascular endothelial cell proliferation is inhibited up to 80% by TGF-beta 1; however, in three-dimensional (3-D) collagen gels TGF-beta 1 is found to have no effect on proliferation while eliciting the formation of calcium and magnesium dependent tube-like structures mimicking angiogenesis. DNA analyses performed on 3-D cell cultures reveal no significant difference in the amount of DNA or cell number in control versus TGF-beta 1 treated cultures. In 2-D cultures TGF-beta 1 is known to increase cellular fibronectin accumulation; however, in 3-D cultures no difference is seen between control and TGF-beta 1 treated cells as established by ELISA testing for type IV collagen, fibronectin, and laminin. In 3-D cultures there is increased synthesis and secretion of type V collagen in both control and TGF-beta 1 treated cultures over 2-D cultures. Even though an equal amount of type V collagen is seen in both 3-D conditions, there is a reorganization of the protein with concentration along an organizing basal lamina in TGF-beta 1 treated cultures. EM morphological analyses on 3-D cultures illustrate quiescent, control cells lacking cell contacts. In contrast, TGF-beta 1 treated cells show increased pseudopod formation, cell-cell contact, and organized basal lamina-like material closely apposed to the "abluminal" plasma membranes. TGF-beta 1 treated cells also appear to form junctional complexes between adjoining cells. Immunofluorescence using specific antibodies to the tight junction protein ZO-1 results in staining at apparent cell-cell junctions in the 3-D cultures. Northern blots of freshly isolated microvascular endothelium, 2-D and 3-D cultures, using cDNA and cRNA probes specific for the ZO-1 tight junction protein, reveal the presence of the 7.8 kb mRNA. Western blots of rat epididymal fat pad endothelial cells (RFC) monolayer lysates probed with anti-ZO-1 label a 220 kd band which co-migrates with the bonafide ZO-1 protein. These data confirm and support the hypothesis that TGF-beta 1 is angiogenic in vitro, eliciting microvascular endothelial cells to form tube-like structures with apparent tight junctions and abluminal basal lamina deposition in three-dimensional cultures.
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PMID:Transforming growth factor beta 1 modulates extracellular matrix organization and cell-cell junctional complex formation during in vitro angiogenesis. 168 59

Functional biological assays were performed using a hybrid molecule of Transforming Growth Factor-Beta (TGF-5 beta) where nine amino acids near the cleavage site of TGF-beta 1 were substituted with nine amino acids located in the identical position of TGF-beta 2. Bovine aortic endothelial and smooth muscle cells as well as rat epididymal fat pad microvascular endothelia were studied in three distinct bioassays examining proliferation, migration and angiogenesis. The data suggested TGF-5 beta elicited results that do not differ significantly from the TGF-beta 1 isoform, while TGF-beta 2 expressed unique characteristics. We have also shown that these amino acid substitutions to TGF-beta 1 do not, in fact, alter the biological functions of the growth factor.
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PMID:Vascular cell responses to a hybrid transforming growth factor-beta molecule. 170 38

The vascular cell responses to the type 3 isoform of transforming growth factor-beta (TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMCs) as well as rat epididymal fat pad microvascular endothelia (RFCs). Four distinct bioassays indicated that TGF-beta 3 elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. Inhibition of proliferation by TGF-beta 3 at a 5-day time point ranged from 85% on BAECs, to 55% and 53% on RFCs and BASMCs, respectively. The effects of TGF-beta 3 and TGF-beta 1 on cell migration were also found to be similar; migration of large vessel endothelial cells was inhibited 35%, while migration of smooth muscle cells was enhanced 30%. TGF-beta 1 and TGF-beta 3 also had equivalent effects on neovascularization while a 10-fold higher concentration of TGF-beta 2 was required to elicit a similar response. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF-beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent upon the cell type examined. In summary, both the TGF-beta 1 and TGF-beta 3 isoforms of the transforming growth factor-beta family evoke comparable responses in proliferation, migration, angiogenic and cell surface binding assays using three distinct vascular cell types, while the biofunctions of TGF-beta 2 on these cells are distinct.
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PMID:Vascular cell responses to TGF-beta 3 mimic those of TGF-beta 1 in vitro. 176 38

Transforming growth factor beta 1 (TGF-beta 1) and beta 2 (TGF-beta 2) are equipotent in many cell systems studies thus far. Recent data, however, show different effects elicited by these two growth factors in specific biologic systems. This investigation compares the effects of TGF-beta 1 and TGF-beta 2 bovine aortic endothelial cells (BAECs), rat epididymal fat pad microvascular endothelium (RFCs), and bovine aortic smooth muscle cells (BASCs). In two-dimensional cultures, proliferation of BAECs, BASMCs, and RFCs were all inhibited by TGF-beta 1, while in response to TGF-beta 2, BASMCs were fully inhibited, RFCs were modestly inhibited, and BAECs were unaffected. Bovine aortic endothelial cell migration was significantly inhibited by TGF-beta 1, but only slightly inhibited by TGF-beta 2. In contrast, BASMC migration was enhanced by TGF-beta 1 and was not affected by TGF-beta 2. In three-dimensional cultures, RFCs were stimulated to undergo in vitro angiogenesis in response to TGF-beta 1 and TGF-beta 2 at 10-fold higher concentrations. Three distinct receptor assays demonstrated the presence of type I and type II TGF-beta 1 cell-surface-binding proteins on BAECs, BASMCs, and RFCs. Labeled TGF-beta 1 was competed off completely with 100-fold molar excess unlabeled TGF-beta 1, but only partially with equivalent excess unlabeled TGF-beta 2. Furthermore the ratios of type I to type II TGF-beta receptors in these three vascular cell types vary from 1:1 in BAECs to 1.5:1 in RFCs to 3:1 in BASMCs and can be correlated with the differences noted in cellular responses to TGF-beta 1 and TGF-beta 2 in proliferation, migration, and in vitro angiogenic assays. These findings support the hypothesis that there are different responses to the TGF-beta s, depending on the cell type and experimental conditions as well as the TGF-beta concentration and isoform used.
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PMID:Vascular cells respond differentially to transforming growth factors beta 1 and beta 2 in vitro. 184 64

Recent studies of whole animal responses have defined a role for circulating TGF-beta in the preservation and stabilization of microvascular endothelial function (Lefer et al. [1993] Proc. Natl. Acad. Sci. U.S.A., 90:1018-1022; Pfister et al. [1992] J. Exp. Med., 176:265-269). In order to determine which TGF-beta receptor types are responsible for this endothelial cell responsiveness, we used an affinity-labeling technique with 125I-TGF-beta 1 and -beta 2 to characterize TGF-beta receptors on five different endothelial cell cultures: early passage bovine lung and rat epididymal fat pad microvascular endothelial cells (BLMEC and REEC), established endothelial cell lines from bovine adrenal medulla capillaries (EJG), fetal bovine heart (FBHE), and bovine pulmonary artery (CPAE). Since it is known that endothelial cells from different parts of the vasculature vary with respect to cell surface antigen expression (McCarthy et al. [1991] Trends Pharmacol. Sci., 12:462-467; Augustin et al. [1994] Bioessays, 16:901-906), it is important to compare TGF-beta receptor expression on microvascular and macrovascular endothelial cells. We observed 85 kDa and 200-400 kDa labeled receptor bands and analyzed their relationship to the cloned Type II and III receptors using peptide antibodies. We used dithiothreitol and phosphoinositol-phospholipase C pretreatments to establish whether the 65 kDa labeled band which we observed corresponded to the Type I receptor or a glycophosphotidylinositol-linked binding protein. The results demonstrated that microvascular but not macrovascular endothelial cells express high levels of the Type III receptor. This differential expression of the Type III receptor indicates that distinct anatomical segments of the vasculature have distinct TGF-beta receptor profiles. The presence of the Type III receptor on micro- but not macrovascular endothelial cells may account for the reportedly different potency of TGF-beta 1 and TGF-beta 2 on these two endothelial cell types. Analysis of the 85 kDa and 65 kDa affinity-labeled bands revealed that all the endothelial cells express the Type II receptor and a band consistent with the presence of a dithiothreitol-sensitive Type I receptor. Two isoform-specific phosphoinositol-phospholipase C releasable TGF-beta binding proteins were also detected: a 60 kDa protein on one micro- (EJG) and one macro- (FBHE) vascular endothelial cell line and a 150/180 kDa protein on the macrovascular cell lines (FBHE and CPAE). These studies emphasize the heterogeneous nature of endothelial cells and underline the importance of using microvascular endothelial cells when examining TGF-beta responses related to microvascular function.
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PMID:Transforming growth factor-beta receptor expression on endothelial cells: heterogeneity of type III receptor expression. 755 2

The transforming growth factor-beta1 (TGF-beta1) and the transforming growth factor-beta receptor type II (TGF-betaRII) were studied in the epididymis of sexually mature marmoset monkeys (Callithrix jacchus) by immunohistochemical localization of the protein and by polymerase chain reaction (PCR) analysis of the mRNA level. In order to specify reactive cell types, the morphology of all three segments (caput, corpus, and cauda epididymidis) was evaluated by light microscopy. Six different cell types could be distinguished: principal, basal, apical, and clear cells, as well as intraepithelial lymphocytes and macrophages. Using immunohistochemistry, specific staining for TGF-beta1 in the caput was found in 47% of the apical cells, whereas the TGF-betaRII was located in the apical portion of 91% of all principal cells. In the corpus epididymidis, 20% of the apical cells were immunopositive for TGF-beta, and binding of the receptor antibody occurred in 17% of the principal cells (all numbers based on counts of counterstained nuclei). All differences between percentages in the caput and corpus were significant as determined by chi-square test. PCR analysis revealed detectable levels of TGF-beta1 mRNA in the marmoset epididymis. Our results indicate for the first time that TGF-beta1 is synthesized in the marmoset epididymis, possibly in a different subpopulation of epididymal cells than the TGF-beta receptor type II. Thus, TGF-beta might be of functional relevance in the primate epididymis.
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PMID:TGF-beta could be involved in paracrine actions in the epididymis of the marmoset monkey (Callithrix jacchus). 1038 17

Microencapsulation of islets of Langerhans within semipermeable membranes has been proposed to prevent their immune destruction after transplantation. However, the successful application of this method is impaired by a pericapsular reaction, which eventually induces graft failure. Our goal is to study the role of cytokines in the pathogenesis of this reaction, using the model of alginate-poly-L-lysine microcapsule implantation into Wistar rat epididymal fat pads (EFP). The specific objective of this study was to determine the time course of transforming growth factor (TGF)-beta(1) mRNA expression by semi-quantitative reverse transcriptase-polymerase chain reaction. Microcapsules induced an increase of TGF-beta(1) mRNA expression that reached a maximum 14 days after implantation. Seven, 14, 30, and 60 days after microcapsule implantation, the expression of TGF-beta(1) mRNA was significantly higher in pericapsular infiltrate cells than in nonimplanted EFP cells (p<0.05, p<0.0001, p<0.005, and p<0.01, respectively). Injection of physiological saline induced a small and gradual augmentation of TGF-beta(1) mRNA expression with a maximum 30 days after injection (p<0.01 vs. nonimplanted EFP cells). These results demonstrated that microcapsule implantation, in comparison with saline injection, induce an early, extended, and amplified TGF-beta(1) mRNA expression. This suggests that TGF-beta(1) plays a role in the pathogenesis of the pericapsular host reaction.
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PMID:Time course of transforming growth factor-beta(1) (TGF-beta(1)) mRNA expression in the host reaction to alginate-poly-L-lysine microcapsules following implantations into rat epididymal fat pads. 1090 70

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the formation of estrogens from androgens. According to the age, aromatase activity has been measured in immature and mature rat Leydig cells, as well as in Sertoli cells whereas in pig, ram and human the aromatase is mainly present in Leydig cells. In the rat testis, we have immunolocalised the P450arom not only in Leydig cells but also in germ cells and especially in elongated spermatids. Related to the stage of germ cell maturation, we have shown that the level of P450arom mRNA transcripts decreases, it is much more abundant in younger than in mature germ cells whereas the aromatase activity is two- to four-fold greater in spermatozoa when compared to the two other enriched-germ cell preparations. Moreover, we have reported the existence of alternative splicing events of P450arom mRNA in pachytene spermatocytes and round spermatids giving rise to two isoforms lacking the last coding exon which, therefore, cannot encode functional aromatase molecules. In rat germ cells, the aromatase gene expression is not only under androgen control but also subjected to cytokine (TNFalpha) and growth factor (TGFbeta) regulation. In the bank-vole testis, we have evidenced a synchronisation between a fully developed spermatogenesis and a strong positive immunoreactivity for both P450arom and estrogen receptor (ERbeta) in spermatids. Therefore, the aromatase gene expression and its translation in a fully active protein in rodent germ cells evidence an additional site for estrogen production within the testis. Our recent data showing that human ejaculated spermatozoa expressed specific transcripts for P450arom reinforced the observations reported in germ cells of other mammalian species. Together with the widespread distribution of ERs in testicular cells these data bring enlightenments on the hormonal regulation of male reproductive function. Indeed these female hormones (or the ratio androgens/estrogens) do play a physiological role (either directly on germ cells or via testicular somatic cells) in the maintenance of male gonadal functions and obviously, several steps are concerned particularly the spermatid production and the epididymal sperm maturation.
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PMID:Aromatase expression in male germ cells. 1185 Feb 26

Macrophage inhibitory cytokine-1 (MIC-1), a divergent member of the TGF-beta superfamily, is involved in the control of multiple cellular processes and mediates cachexia through the inhibition of appetite. Adipose tissue as an endocrine organ secretes proteins (adipokines) that regulate energy homeostasis and other cellular functions. This study investigated whether MIC-1 is expressed in adipose tissue and whether MIC-1 is a secretory product of adipocytes. Mouse and human adipose tissues were collected from different depots. 3T3-L1 preadipocytes and human preadipocytes were induced to differentiate into adipocytes in cell culture. MIC-1 mRNA was detected in the major mouse adipose depots (epididymal, perirenal, sc). In these depots, MIC-1 gene expression was evident in both isolated mature adipocytes and stromal-vascular cells. In 3T3-L1 adipocytes, MIC-1 mRNA was detected before and after differentiation. MIC-1 mRNA and protein secretion were evident in human preadipocytes as well as differentiated adipocytes. MIC-1 production by human adipocytes was stimulated by H(2)O(2) and 15d-prostaglandin J(2). In addition, recombinant MIC-1 increased adiponectin secretion by differentiated human adipocytes. MIC-1 mRNA and protein were also observed in human sc and visceral fat. MIC-1 mRNA levels were positively correlated with adiponectin mRNA. Moreover, MIC-1 mRNA was negatively associated with body mass index and body fat mass in human subjects. We conclude that MIC-1 is expressed in adipose tissue and secreted from adipocytes and is therefore a new adipokine. MIC-1 may have a paracrine role in the modulation of adipose tissue function and body fat mass.
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PMID:Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. 1907 84

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