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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroglobin is a progesterone binding protein, a member of the antiflammin gene family and possibly a novel cytokine. Initially, uteroglobin was identified as the major protein of rabbit uterine secretion during the phase of preimplantation. Counterparts of the rabbit uteroglobin or its gene are described in rat, mouse, hamster, hare, pig, horse and human. While uteroglobin appears as one of the most extensively studied proteins, particularly its physico-chemical properties, including its crystal structure and its gene, the true physiological role of this protein still remains to be unravelled. Essential to understanding the significance of human uteroglobin in reproductive organs, particularly in the endometrium, is a knowledge of the spatial and chronological expression of this secretory protein. Our studies on 115 volunteers combined reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and quantitative assessment by an enzyme-linked immunosorbent assay for uteroglobin. The expression, localization and release of uteroglobulin in the human endometrium are presented. Secretory uteroglobin is found in endometrial tissue homogenates in highest levels of expression during the early luteal phase (days 15-19, 340 pg/mg total protein). In turn, uteroglobin is released into the uterine lumen in peak amounts during the receptive phase of the menstrual cycle (mid-luteal phase, days 20-23, secretion level 833.4 pg/mg total protein). Our immunohistochemical studies match with these results, as uteroglobin is located during the early and mid-luteal phase in the apical compartments of endometrial gland cells. These observations strongly suggest an involvement of uteroglobin in endometrial preparations for implantation.
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PMID:Expression of uteroglobin in the human endometrium. 1058 71

Uteroglobin gene-disrupted mice develop a nephritis very similar to immunoglobulin A (IgA) nephropathy. Megsin codes for a protein overexpressed in mesangium in patients with IgA nephropathy. Both are candidate genes that might have variants associated with an accelerated progression in patients with IgA nephropathy. We performed an association study of patients with IgA nephropathy and matching control subjects to test whether the G38A polymorphism in the uteroglobin gene, the C2093T polymorphism in the megsin gene, or the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is associated with IgA nephropathy or rate of disease progression in patients with IgA nephropathy. Of 110 patients with IgA nephropathy, 87 patients were followed up for at least 3 years for the progression study. We also studied 104 healthy volunteers. The uteroglobin, megsin, and ACE polymorphisms were not distributed differently in the 110 patients with IgA nephropathy compared with healthy controls; Hardy-Weinberg equilibrium criteria were fulfilled. The GG genotype of the G38A uteroglobin polymorphism was more common in patients with progression (odds ratio [OR], 3.5; P< 0.006) than the AG+AA genotypes. The G allele was also more common (OR, 2.6; P< 0.009) in patients with versus without progression. The 1/serum creatinine over time plot (in deciliters per milligram per day) was sevenfold steeper in GG patients than the other two genotypes (P = 0.08). No significant associations with disease progression were found for the other gene polymorphisms, and a multivariate analysis showed no interactions. We suggest the hypothesis that the uteroglobin gene contains variant(s) with a bearing on progression rate in patients with IgA nephropathy.
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PMID:Association of a uteroglobin polymorphism with rate of progression in patients with IgA nephropathy. 1097 77

Uteroglobin, originally named blastokinin, is a protein synthesized and secreted by most epithelia, including the endometrium. Uteroglobin has strong anti-inflammatory properties that appear to be due, at least in part, to its inhibitory effect on the activity of the enzyme phospholipase A(2). In addition, recent experimental evidence indicates that uteroglobin exerts antiproliferative and antimetastatic effects in different cancer cells via a membrane receptor. The human endometrial adenocarcinoma cell line HEC-1A does not express uteroglobin. Thus, we transfected HEC-1A cells with human uteroglobin cDNA. The transfectants showed a markedly reduced proliferative potential as assessed by impaired plating efficiency as well as by reduced growth in soft agar. Cytofluorimetric analysis clearly indicated that in uteroglobin-transfected cells the time for completion of the cell cycle was increased. We previously demonstrated that HEC-1A cells actively synthesize platelet-activating factor, one of the products of phospholipase A(2) activity. In addition, we demonstrated that platelet-activating factor stimulates the proliferation of these cells through an autocrine loop. In uteroglobin transfectants, the activity of phospholipase A(2) and platelet-activating factor acetyl-transferase, which are involved in the synthesis of platelet-activating factor, was significantly reduced compared with wild-type and vector-transfected cells (p < 0.05). Our results indicate that enforced expression of uteroglobin in HEC-1A cells markedly reduced their growth potential and significantly impaired the synthesis of platelet-activating factor, an autocrine growth factor for these cells. These data suggest that one possible mechanism for the recently observed antineoplastic properties of uteroglobin may be the inhibition of the synthesis of platelet-activating factor.
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PMID:Uteroglobin reverts the transformed phenotype in the endometrial adenocarcinoma cell line HEC-1A by disrupting the metabolic pathways generating platelet-activating factor. 1105 67

Uteroglobin, a steroid-inducible, cytokine-like, secreted protein with immunomodulatory properties, has been reported to bind progesterone, polychlorinated biphenyls (PCB), and retinol. Structural studies may delineate whether binding of ligands is a likely physiological function of human uteroglobin (hUG). We report a refined crystal structure of uncomplexed recombinant hUG (rhUG) at 2.5-A resolution and the results of our molecular modeling studies of ligand binding to the central hydrophobic cavity of rhUG. The crystal structure of rhUG is very similar to that of reported crystal structures of uteroglobins. Using molecular modeling techniques, the three ligands--PCB, progesterone, and retinol--were docked into the hydrophobic cavity of the dimer structure of rhUG. We undocked the progesterone ligand by pulling the ligand from the cavity into the solvent. From our modeling and undocking studies of progesterone, it is clear that these types of hydrophobic ligands could slip into the cavity between helix-3 and helix-3' of the dimer instead of between helix-1 and helix-4 of the monomer, as proposed earlier. Our results suggest that at least one of the physiological functions of UG is to bind to hydrophobic ligands, such as progesterone and retinol.
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PMID:Crystal structure analysis of recombinant human uteroglobin and molecular modeling of ligand binding. 1119 50

Uteroglobin/Clara cell 10-kDa protein (UG/CC10) is a hormonally regulated small secretory protein that has a variety of in vitro and in vivo pharmacological effects. These include a potent anti-inflammatory activity and inhibitory effects on neutrophil migration, thrombin-induced platelet aggregation, in vitro chemoinvasion, as well as "tumor suppressor"-like effects and other properties. Several mechanisms of action have been proposed for these effects. Pharmacological properties suggest that UG itself or substances derived from it may be used as experimental drugs for several indications. The group of oligopeptides collectively known as "antiflammins" (AFs) were originally described in 1988. Their design was derived from the region of highest sequence similarity between UG and another group of proteins with anti-inflammatory properties, the lipocortins or annexins. Nanomolar concentrations of these peptides can reproduce several of the pharmacological activities of UG, including its in vivo anti-inflammatory effects and inhibition of platelet aggregation. The AFs have been safely and effectively used to suppress inflammation and fibrosis in several animal models. Progress in clarifying the mechanism of action of the AFs may facilitate the structure-based design of a novel class of potent anti-inflammatory, antichemotactic drugs.
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PMID:Antiflammins. Bioactive peptides derived from uteroglobin. 1119 51

Uteroglobin/CCSP is expressed specifically in the Clara cells. This allows the gene to be used as a marker to identify the elements regulating the physiologic and cell-specific expression of this gene. The regulation of UG/CCSP by IFN-gamma was shown to be at the level of the proximal promoter by the upregulation of HNF3 beta. This has allowed the determination of the factors responsible for the expression of UG/CCSP.
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PMID:Physiological regulation of uteroglobin/CCSP expression. 1119 56

The discovery of uteroglobin resulted from investigations on the biochemical composition of oviductal and uterine secretions of the rabbit and other mammals. These determinations about physiological composition were urgently requested to prepare culture media for research on early mammalian development in vitro. Discovery of significant proteins during the sixties reflected the laboratory skills of that time. Protein characterization was achieved by isolation via Sephadex gels, electrophoresis on polyacrylamide gels, and finally immunoprecipitation using classical polyclonal antibodies. The molecular biology was not yet established. Uteroglobin could be found as the major protein component of rabbit uterine secretion. From the beginning, it was already identified as an unusually small, spheric uterine secretory molecule without any carbohydrates--hence its name. Uteroglobin was the first mammalian protein that turned out to be progesterone-regulated and, at the same time, released in mg amounts actually in one organ compartment. Moreover, uteroglobin and its gene proved to be a reliable model for the description of progesterone/progesterone receptor complex action at the DNA level. After its original observation in the uterus, however, uteroglobin was detected also in several other organs, for example, the epididymis, the seminal vesicle, and the lung. Initially, it could not be found in the blood, which challenged the hypothesis that uteroglobin specifically should operate by local activation rather than by a humoral or endocrine effect. Later, though, the human uteroglobin molecule, isolated from blood filtrate, was used for detailed structural analyses. The rabbit uteroglobin model certainly was beneficial for reproductive biological research. Experimental interference with steroid hormone regulation during preimplantation presented surprising effects, which led to the discovery of the transposition of the implantation window. The uterine secretion protein patterns, in particular the uteroglobin fraction and the beta-glycoprotein fraction, served as decisive marker profiles to identify the biological stage of the intrauterine microenvironment during preimplantation. This diagnostic procedure, using only protein parameters, enabled us to precisely predict the receptive stage of the endometrium for donated blastocysts to achieve implantation successfully.
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PMID:The discovery of uteroglobin and its significance for reproductive biology and endocrinology. 1119 82

Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small- to medium-sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the alpha/beta hydrolase family, making it a well-suited "geode" structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity.
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PMID:The uteroglobin fold. 1119 83

Clara cell 10 kilodalton protein(CC10) is the major product of non-ciliated bronchiolar epithelial cells (Clara cells) and is identical with uteroglobin and urinary protein 1(P-1). CC10/uteroglobin is a homodimer consisting of 70 amino acid subunits arranged in an antiparallel fashion and connected by two disulfide bonds. CC10/uteroglobin shows an anti-inflammatory property including inhibition of phospholipase A2 and phospholipase C. We analyzed the epitope of monoclonal antibodies(mAbs) to human CC10/P-1. TY-5, TY-7 and TY-8 recognized alpha 1-, alpha 2- and alpha 3-helix of CC10, respectively. The combination of TY-1 and TY-2 are most suitable for ELISA, while TY-5 and TY-7 are very good for immunoblot and immunohistochemical analysis. Circulating CC10 levels are increased in sarcoidosis and decreased in asthma. Bronchoalveolar lavage CC10 levels are increased in sarcoidosis patients with a good outcome. The use of these mAbs is a powerful tool to investigate the clinical roles of CC10. CC10 is a regulator of the inflammatory process in respiratory diseases.
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PMID:[Anti-inflammatory molecule, Clara cell 10 kilodalton protein and respiratory diseases]. 1201 16

Uteroglobin (blastokinin), a widely studied protein in uterine secretions, is secreted by the glandular epithelium of the uterus in species such as deer or rabbits. It is hypothesized that uteroglobin transports progesterone in uterine secretions implying that protein is produced in response to progesterone, and then it transports the steroid through the uterine lumen. There has been disagreement on the ability of uteroglobin to transport much progesterone and on the strength of binding of the steroid to the protein. Assays of steroids in rabbit uterine fluids hve shown that progesterone levels can be high and follow closely the values for uteroglobin. Most progesterone appears bound to protein; neither estradiol-17beta nor 17alpha-hydroxyprogesterone was detectable in the flushings suggesting that the binding of steroids is highly specific. The debate over the role of uteroglobin continues; there is a possiblity that other proteins in the human uterus similar to uteroglobins may be present and may offer a useful approach for suppressing fertility.
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PMID:Steroids and the secretion of fluid by the uterus. 1233 13


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