Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroglobin (UG) is a multifunctional protein with anti-inflammatory/immunomodulatory properties. The UG gene is located on the long arm of chromosome 11 (11q12.3-q13.1) in a region linked to some immune disorders. A guanine-adenine substitution at position 38 (A38G) has been found in the noncoding region of exon 1 that is significantly correlated with an increased risk of developing immune-mediated diseases. Recently an experimental model of UG knockout mice showed that in mice, UG deficiency causes severe glomerulopathy with mesangial deposition of IgA-fibronectin complexes. To detect the presence of polymorphisms in the UG coding sequence, the DNA of 109 patients with IgA nephropathy (IgAN), and 32 patients with systemic lupus erythematosus (SLE) were tested for the nucleotide sequence of all three UG exons by heteroduplex analysis. We detected heterozygous DNA only for exon 1 due to the A38G substitution, as confirmed by sequencing. We tested for A38G polymorphism, by restriction endonuclease digestion (Sau96I), both in SLE patients and in IgAN patients. Twenty patients with either membranous nephropathy (12) or focal and segmental glomerular sclerosis and 120 healthy subjects served as controls. Compared with both healthy controls and non-IgA control patients, the frequency of the 38A allele was significantly higher in SLE patients (38 of 64 alleles versus 89 of 240 alleles, p = 0.002, and versus 7 of 40 alleles, p < 0.001). IgAN patients showed an allelic distribution similar to both control groups. A subgroup of 18 IgAN patients undergoing renal replacement therapy because of end-stage renal disease showed a significant increase in 38A allele frequency (5 of 36 38G alleles versus 31 of 36 38A alleles, p < 0.001). UG is an immunomodulatory agent that is able to (a) inhibit the activity of several phospholipase A2 (PLA2s), (b) interfere with the function of both neutrophils and monocytes, and (c) prevent immune recognition, perhaps by masking surface antigens. This could account for the role this molecule plays in SLE. The A38G polymorphism is located within a region corresponding to the rat minimal promoter that proved to be important in the transcriptional regulation of UG. Although the significance of any alterations in the UG exon 1 noncoding region in humans has yet to be clarified, initial evidence suggests that it may alter the control of immune response and of inflammation.
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PMID:Polymorphism of the uteroglobin gene in systemic lupus erythematosus and IgA nephropathy. 1200 94

A 78-year-old-man was admitted to our hospital because of renal insufficiency 20 months after the onset of autoimmune pancreatitis. He had cerebral infarction and prostatic hypertrophy as complications. He had been previously diagnosed with autoimmune pancreatitis (AIP). The initial therapy was started with oral prednisolone at the dose of 0.8 mg/kg (40 mg/day). Prednisolone had been tapered off gradually through a one-year period. Four months later from terminating prednisolone, a follow-up CT showed multiple low-density areas in both kidneys without swelling of the pancreas. Furthermore, 4 months later, laboratory findings showed progressive renal insufficiency. On admission, BP was 167/77 mmHg, and the bilateral submaxillary glands were swollen. He did not have pretibial edema. Laboratory findings were as follows. BUN 55.9 mg/dL, Cre 6.17 mg/dL, Amy 65 mg/dL, TP/Alb 9.5/4 g/dL, gamma-gl 43.7%, IgG/IgA/IgM 3,395/112/74 mg/dL, IgG4 1,460 mg/dL, urinary protein 1.38 g/day, and 24 hr-Ccr 11.8 mL/min/1.73 m2. Percutaneous renal needle biopsy was conducted. Light microscopic findings demonstrated tubulointerstitial nephritis (TIN) and membranous change. Immunofluorescent microscopic findings indicated diffuse deposition of IgG2 and IgG4 in the renal interstitium. On the basis of these findings, the condition was diagnosed as IgG4-related tubulointerstitial nephritis. As renal insufficiency was progressing, hemodialysis was started soon after admission and oral prednisolone was also started at the dose of 0.4 mg/kg (20 mg/day). However, improvement of renal function has not been obtained and hemodialysis and prednisolone tapering are still being conducted. This case showed severe tubulointerstitial nephritis requiring hemodialysis after a cure for autoimmune pancreatitis. IgG4-related renal disease rarely needs hemodialysis. This case indicates that the prognosis of IgG4-related systemic disease is not necessarily good and further accumulation of cases is required.
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PMID:[Case of IgG4-related tubulointerstitial nephritis showing the progression of renal dysfunction after a cure for autoimmune pancreatitis]. 2016 45

Serum amyloid A (SAA) production is increased by inflamed arthritic synovial tissue, where it acts as a cytokine/chemoattractant for inflammatory and immune cells and as an inducer of matrix degrading enzymes. SAA has been shown to bind lipoxin A4 receptor, a member of the formyl-peptide related 2 G-protein coupled receptor family (ALX) and elicit proinflammatory activities in human primary fibroblast-like synoviocytes (FLS). We report on the identification of uteroglobin, a small globular protein with potent anti-inflammatory activities, as a possible ligand of ALX. Uteroglobin-specific association with ALX was demonstrated by an enzyme immunoassay experiment employing a cell line engineered to express the human ALX receptor. Uteroglobin's interaction with ALX resulted in the inhibition of SAA responses, such as attenuation of phospholipase A2 activation and cellular chemotaxis. In FLS, uteroglobin showed an antagonism against SAA-induced interleukin-8 release and decreased cell migration. These novel roles described for uteroglobin via ALX may help elucidate genetic and clinical observations indicating that a polymorphism in the uteroglobin promoter is linked to disease outcome, specifically prediction of bone erosion in patients with rheumatoid arthritis or severity of IgA glomerulonephritis and sarcoidosis.
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PMID:Uteroglobin, a possible ligand of the lipoxin receptor inhibits serum amyloid A-driven inflammation. 2478 97