Disease relevance of SCGB3A2

• CCSP, SCGB3A1, and SCGB3A2 were decreased in airways of neonates with bronchopulmonary dysplasia and in mice after airway injury [1].
• By in situ hybridization experiments, UGRP1 was shown to be expressed by lung Clara-like cells in the bronchial epithelium and to be up-regulated in cystic fibrosis [2].
• Measurements and main results: Sputum UGRP1 increased in both asthma and rhinitis, most strikingly so in asthma, in which changes were most significant in atopic individuals [3].
• We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S. pneumoniae (MRSP), and macrolide-resistant S. pyogenes (MRGAS) in 20 countries [4].
• Independently significant risk factors associated with PNSP bacteremia were sepsis and prior treatment with beta-lactam antibiotics [5].

High impact information on SCGB3A2

• UGRP1 is a homodimeric secretory protein of 17 kDa and is expressed only in lung and trachea [6].
• In the present article, we describe UGRP1 (encoding uteroglobin-related protein 1) as one of asthma-susceptibility genes that is located on chromosome 5q31-q32 [6].
• This IL-10 induction of Ugrp1 gene expression occurs at the transcriptional level when examined using mouse embryonic lung primary cultures [7].
• Our findings suggest that UGRP1-MARCO is a ligand-receptor pair that is probably involved in inflammation and pathogen clearance in the lung [2].
• In a mammalian expression system, secreted recombinant UGRP1 was copurified with apolipoprotein A-I [2].

Biological context of SCGB3A2

• This gene, designated Ugrp1 (uteroglobin-related protein 1), consists of three exons and two introns and produces three transcripts by alternative splicing [8].
• The Ugrp1 gene was localized by fluorescence in situ hybridization to mouse chromosome 18 at region 18C-D; this region is homologous with human 5q31-34, where one of the asthma susceptibility genes has been assigned [8].
• The nationwide sentinel surveillance of nasopharyngeal pneumococcus proved to be valuable for the monitoring of antibiotic resistance, risk factors for carriage of PNSP isolates, and serotype distribution and for the detection of the emergence of a new epidemic clone [9].
• To determine the epidemiology of bacteremias due to pneumococci not susceptible to penicillin (PNSP) at a university hospital, active microbiologic surveillance of bacteremias due to PNSP was done for 28 months [5].
• The ORF of this UGRP cDNA encodes a protein (346 amino acids (aa); M(r) 38 709) which shares 36% overall identity to the human G6Pase catalytic subunit (357 aa; M(r) 40 487) [10].

Anatomical context of SCGB3A2

• UGRP1 mRNA is predominantly expressed in the lung, with low levels of expression in the thyroid [8].
• Changes in sputum UGRP1 in atopic asthma were not linked to permeability changes reflected by increased albumin levels but correlated positively with sputum macrophages and negatively with eosinophils [3].
• The overall rate of penicillin-nonsusceptible pneumococcal (PNSP) strains was 11%; specific prevalence rates, according to the sources of the isolates, were as follows: blood, 6%; cerebrospinal fluid, 10%; lower respiratory tract, 10%; and middle ear, 18% [11].
• In contrast to the G6Pase catalytic subunit gene promoter, the UGRP promoter was highly active in all cell lines examined [10].
• Among PNSP only 2 strains were isolated from sterile body fluids, one having MIC >3.84 mg/l. Lack of susceptibility to cotrimoxazole was 38.4% [12].

Associations of SCGB3A2 with chemical compounds

• Twelve PNSP were resistant to other drugs: chloramphenicol (5), tetracycline (6), trimethoprim-sulfamethoxazole (5), cefotaxime (1), and erythromycin (1) [5].
• The aims of this study were to evaluate the resistance patterns and serotypes/groups of penicillin non-susceptible pneumococci (PNSP) in Finland, and to determine phenotypes and resistance mechanisms of the erythromycin-resistant isolates [13].
• The was a significant correlation between antibiotic use and the proportion of PNSP (correlation coefficient, 0.96; P = 0.002), and the correlation coefficients for trimethoprim-sulfamethoxazole, amoxicillins, macrolides and cephalosporins were significant at the 0.001 level [14].
• There was no significant correlation between the use of penicillin V and the frequency of PNSP [14].
• Most of the penicillin-nonsusceptible S. pneumoniae (PNSP) were also nonsusceptible to other antibiotics except cefotaxime, and imipenem [15].

Other interactions of SCGB3A2

• SCGB3A1 messenger RNA localizes to a subset of SCGB3A2-expressing cells within bronchi of both mouse and neonatal human lungs [1].
• By contrast, sputum CC16 did not change significantly in either condition, although it was positively correlated with UGRP1 in patients and control subjects [3].
• Using a retroviral vector-mediated expression cloning approach, we identified macrophage scavenger receptor with collagenous structure (MARCO) as a receptor for UGRP1 [2].
• The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation [16].

Analytical, diagnostic and therapeutic context of SCGB3A2

• In vivo experiments using mouse embryonic lung organ culture and intranasal administration of interleukin (IL) 10 revealed that constitutive expression of Ugrp1 mRNA is enhanced by IL-10 [7].
• 5. In T/ebp/Nkx2.1-null embryo lungs, UGRP1 expression was significantly reduced as assessed by RT-PCR analysis [8].
• Northern blot analysis demonstrated that UGRP1 is specifically expressed by lung, but not by the other tissues examined [2].
• PFGE typing and serotyping suggest that the frequency of PNSP in the San Antonio, Texas, area is not due to dissemination of a single clonal strain [5].
• Niimi et al. showed the -112G/A polymorphism of the UGRP1 gene to be associated with asthma in a case-control study [17].

References