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

Uteroglobin is a small steroid-binding protein that is differentially regulated by steroid hormones in several tissues of the rabbit. In endometrium, the levels of uteroglobin mRNA increase after progesterone administration due to an enhanced rate of transcription of the uteroglobin gene. As a prerequisite for understanding the molecular mechanisms that modulate uteroglobin gene expression, we have isolated and characterized the uteroglobin gene. We first synthesized, cloned, and sequenced a uteroglobin cDNA that was used to screen a rabbit gene library and to show that the uteroglobin gene is not reiterated in the rabbit genome. We obtained three recombinant phages containing uteroglobin gene sequences and covering 35 kilobases of the rabbit genome. The uteroglobin gene is 3 kilobases long and is composed of three short exons separated by a long and a short intron. The complete coding sequence, the short intron, part of the large intron, and the flanking sequences have been subjected to sequence analysis. The salient features of the nucleotide sequence, including the absence of a canonical "T-A-T-A box," are discussed. A possible relationship is considered between the exon-intron structure of the gene and the known structure and function of uteroglobin.
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PMID:Isolation and structure of the gene for the progesterone-inducible protein uteroglobin. 695 97

1. Uteroglobin-like antigens were found in the lung and uterus of the hare (Lepus) and the pika (Ochotona). These antigens presented an immunoreactivity indistinguishable from that of rabbit uteroglobin, as determined by radioimmunoassay. 2. The molecular weight and the subunit composition of these antigens were similar to those of rabbit uteroglobin as analyzed by SDS gel-electrophoresis. 3. Similar amounts of uteroglobin-like immunoreactivity were found in the respective lungs and uteri of hare and rabbit whereas the concentration of immunoreactivity in the pika organs was several-fold lower.
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PMID:Uteroglobin-like antigens in species of Lagomorpha. 706 7

Uteroglobin is a predominant protein in the rabbit uterus, where it is induced by progesterone, and occurs also in the lung, where its level is constitutive. A recombinant plasmid containing uteroglobin complementary DNA (cDNA) has been constructed previously from partially purified uteroglobin mRNA. In this study, the cloned uteroglobin cDNA has been used as a probe to determine the cellular content of uteroglobin mRNA at different times in early pregnancy in both rabbit uterus and lung. By RNA-excess hybridization to poly A-enriched RNA and to total nucleic acid extracts an increase in steady-state uteroglobin mRNA level was detected, from approximately 250 molecules/uterine epithelial cell in non-pregnant rabbits to approximately 6800 molecules/cell on day 4 of pregnancy, after which the levels declined progressively up to day 8. The pulmonary level of uteroglobin mRNA was about 400 molecules/cell and did not change significantly with day of pregnancy. The major factor in regulating the production of uteroglobin in the uterus of pregnant rabbits is the accumulation and subsequent depletion of its mRNA.
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PMID:Hybridization analysis of steady-state levels of uteroglobin mRNA in rabbit uterus and lung during early pregnancy. 711 50

The physiological androgen, 5 alpha-dihydrotestosterone (DHT), enhances a progesterone-regulated protein (uteroglobin) synthesis in the rabbit uterus. In order to clarify the induction mechanism(s), rabbits were treated for 5 days with DHT alone or concomitantly with a nonsteroidal antiandrogen, RU 23908, or with different doses of estradiol. Uteroglobin content was measured in the uterine fluid by radioimmunoassay and uteroglobin mRNA activity in uterine tissues using cell-free translation in vitro. Uteroglobin induction elicited by DHT was inhibited by a small dose of estradiol, but not by antiandrogen. These results support the idea tha androgens bring about their action on uteroglobin synthesis via a mechanism involving uterine progesterone receptor.
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PMID:5 alpha-Dihydrotestosterone-induced uteroglobin synthesis in rabbit uterus is not inhibited by antiandrogen administration but is prevented by estradiol. 728 83

The synthesis of uteroglobin in rabbit lung was studied after the administration of glucocorticoids to intact adult animals as well as during the late stages of rabbit development. The synthesis of uteroglobin was compared with levels of translatable uteroglobin mRNA in the lung. Uteroglobin synthesis was determined both by incorporation of [25S]methionine into the protein by lung explants incubated in vitro and by radioimmunoassay measurements of uteroglobin concentration in lung. Lung poly(A)-containing mRNA, isolated by oligo(dT)--cellulose chromatography, was translated in cell-free systems and the activity of uteroglobin mRNA was determined after immunoprecipitation. Dexamethasone administration increased about 2-fold the synthesis of lung uteroglobin compared with the controls. The effect of cortisol was more moderate. Both glucocorticoids did not affect the degradation rate of lung uteroglobin, but produced increases in the translatable levels of uteroglobin mRNA parallel to those observed for uteroglobin synthesis. During the late stages of rabbit development, both the synthesis of lung uteroglobin and the translatable levels of its mRNA increase in parallel about 12-fold in a biphasic fashion. A first increase occurred between 2 days before and 2 days after birth. Starting at 5 days of age, there was a second increase in both parameters, which at 12 days of age reached values close to those observed in adult rabbits. Our results suggest that the rate of lung uteroglobin synthesis could be mainly determined by the translatable levels of its mRNA.
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PMID:Glucocorticoid and developmental regulation of uteroglobin synthesis in rabbit lung. 734 64

Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein protects the embryos from maternal immunological assault, facilitates the maintenance of quiescence in the uterus throughout pregnancy, prevents the onset of premature labor, and helps maintain an inflammation-free respiratory organ. This latter function of UG is suggested to be accomplished by preventing hydrolysis of surfactant phospholipids by a lung-specific phospholipase A2. Using reverse transcription polymerase chain reaction, in situ hybridization, immunofluorescence, and radioimmunoassay, we studied UG gene expression in the rabbit uterus throughout gestation and in the fetal lung. Here, we report that: (a) contrary to previous reports, UG gene expression in the rabbit uterus occurs throughout gestation with a precipitous decline just before parturition; (b) this gene expression is dramatically increased in the fetal lung with increasing gestational age; and (c) while there is an inverse relationship between the levels of UG, PGE2, and PGF2 alpha, a positive correlation was found in that of UG and leukotriene C4 in the fetal lung. Our results raise the possibility that dysregulation of UG gene expression, at least in part, may contribute to the onset of premature labor and the development of inflammatory lung disease in premature neonates.
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PMID:Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung. 761 4

One hundred male insulin-dependent diabetic patients, aged 16 to 85 (mean 51.9) years, with albumin excretion ranging from normal to gross excess were examined for glomerular and tubular functional alterations by estimating urinary levels of albumin and indicator proteins of tubular damage. Urine protein 1 (UP1), a newly-discovered low-molecular weight alpha-2 glycomicroglobulin, together with alpha 1-microglobulin was used to assess tubular function. 19% of the patients showed increased albumin excretion with normal levels of tubular proteins (glomerular proteinuria), 11% excreted only tubular proteins in excess (tubular proteinuria), while 40% had a mixed pattern of both increased albumin and tubular proteins (glomerulotubular or mixed proteinuria). 30% had normal albumin and tubular protein excretion in urine. UP1 was found to be a more sensitive indicator of tubular abnormality than alpha 1-microglobulin. It is concluded that, although glomerular changes may be responsible for the proteinuria seen in most diabetics (mixed proteinuria), in a small but significant proportion of diabetics, tubular functional alteration may occur before, or in the absence of, glomerular dysfunction, and may warn of subclinical tubular abnormality. This finding may have a direct bearing on the development and course of progression of diabetic nephropathy, and may question the reliability of the present prognostic interpretation of microalbuminuria.
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PMID:The use of urine protein 1 as an indicator of renal tubular function in type I (insulin-dependent) diabetes. 763 47

The Clara cell phospholipid-binding protein, previously referred to as CC10, is a homodimeric protein of M(r) 15,800. It is secreted into the bronchioalveolar lining layer in mammalian lung. A combination of X-ray crystallography and chemical analysis was used to determine that phosphatidylcholine and phosphatidylinositol are bound to the protein as isolated from human lung lavage. We now report the crystal structure of the protein-phospholipid complex at 1.9 A resolution. The phospholipid is bound inside the protein's large hydrophobic cavity. A model is proposed for the manner in which a channel may open to provide access to the cavity, allowing the binding or potential release of phospholipid.
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PMID:Structure of a human Clara cell phospholipid-binding protein-ligand complex at 1.9 A resolution. 766 82

Lung cancer is a leading cause of tumor-related deaths in humans but its origin and development are poorly understood. To study the biology of these tumors, appropriate animal and cell culture models will be of eminent importance. Uteroglobin is a marker protein for the nonciliated epithelial Clara cells lining the respiratory and terminal bronchioli of the lung. We have used the promoter and 5'-flanking sequences of the rabbit uteroglobin gene to target expression of the SV40 T antigen to the lung of transgenic mice. All transgenic founders as well as the descendants from an established line, UT7.1, developed multifocal bronchioloalveolar adenocarcinomas originating from Clara cells. At least three different stages in tumor development with progressive loss of the differentiated phenotype can be distinguished by immunohistochemical data and in situ hybridization. Only in the initial stage did bronchiolar cells express both uteroglobin and SV40 T antigen, whereas at later stages, only SV40 T antigen was detected, and the most advanced tumors were negative for both proteins. Starting from the lungs of UT7.1 mice, a bronchiolar cell line was established that maintains the features of differentiated Clara cells. This system provides a useful model for further studying the development and progression of lung adenocarcinomas in vivo and in vitro.
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PMID:A transgenic mouse model for lung adenocarcinoma. 771 90

Uteroglobin (UG) is a potent immunomodulatory and antiinflammatory secretory protein with high levels detected in human prostate tissue. We used three human prostate cancer cell lines (DU-145, PC3-M, and LNCaP) to test the hypothesis that UG may modulate invasiveness of prostatic carcinoma cells in the Boyden chamber assay for invasion through a reconstituted basement membrane preparation. Fibroblast-conditioned medium was used as the chemoattractant. The most invasive cell line was DU-145, followed by PC3-M, whereas the androgen-dependent LNCaP cell line exhibited extremely low invasive potential. Pretreatment of DU-145 and PC3-M cells for 24 h with 0.01, 0.1, or 1.0 microM recombinant UG had no effect on basal invasiveness but inhibited fibroblast-conditioned medium-stimulated invasion in a dose-dependent manner, reaching up to 60.2 and 87.9% inhibition of DU-145 and PC3-M, respectively. UG had no effect on either cell-reconstituted basement membrane adhesion or simple chemotaxis in the absence of reconstituted basement membrane. UG also strongly inhibited the biphasic release of [14C]-labeled arachidonic acid from fibroblast-conditioned medium-stimulated DU-145 cells. These results suggest that UG may modulate prostate tumor cell invasiveness and that the mechanism may include inhibition of the arachidonic acid signal cascade.
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PMID:Recombinant human uteroglobin inhibits the in vitro invasiveness of human metastatic prostate tumor cells and the release of arachidonic acid stimulated by fibroblast-conditioned medium. 803 85


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