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Secretoglobin Family 3A Member 2 (Pneumo secretory protein 1, PnSP-1, Uteroglobin-related protein 1, SCGB3A2, Secretoglobin 3A2)

Secretoglobin 3A2 (Secretoglobin family 3A member 2; gene scgb3A2; synonym: uteroglobin-related protein 1, UGRP1) is a homodimeric secretory protein thought to play a role in the modulation of inflammation and tumorigenesis. The human SCGB3A2 gene encodes a protein of molecular weight 10.2 kDa consisting of 93 amino acids, of which the N-terminal 21 amino acid residues exhibit a characteristic signal sequence that may function to target the protein to a secretory pathway. SCGB3A2 is a member of secretoglobin superfamily, a family of small, secreted proteins found in animals exclusively of mammalian lineage. There are 11 human SCGB genes and five pseudogenes. SCGB3A2 mRNA was shown to be predominantly expressed in the lung (predominantly in club cells), with low levels of expression in the thyroid. SCGB3A2 has been demonstrated as a novel growth factor accelerating lung development during both early and late developmental stages. Screening for sequence variations in the exons and the 5´ promoter region of the SCGB3A2 gene among patients with asthma and healthy control individuals revealed the presence of a point mutation, in the promoter region, that appears to be responsible for reduced transcriptional activity of the gene and is associated with an increased risk of asthma. Model mice for allergic airway inflammation were intranasally administered recombinant adenovirus that express SCGB3A2, and the effect of overexpressed SCGB3A2 on antigen-induced airway inflammation was investigated. The results provide evidence that up-regulation of SCGB3A2 in the airways can suppress allergic airway inflammation. In the mouse model, recombinant human SCGB3A2 exhibited anti-fibrotic and growth factor activities comparable to those of recombinant mouse SCGB3A2. These results suggest that SCGB3A2 may have a potential to be used as a therapeutic agent in treating patients suffering from lung diseases or promoting lung development in premature infants in future. SCGB3A2 protein, unlike club cell protein, increases in sputum in asthma and rhinitis. SCGB3A2 mRNA expression was shown to be induced by Th1 cytokine, but suppressed by proinflammatory and Th2 cytokines. SCGBs mRNA expression was altered in chronic rhinosinusitis; particularly, SCGB3A2 protein and mRNA expression was markedly decreased in chronic rhinosinusitis with or without nasal polyps. A recent meta-analysis indicated a significant correlation between SCGB3A –112G/A polymorphism and asthma for AA versus GG (P=0.01) and AA versus GA/GG (P=0.02). Stratification by ethnicity confirmed this result only in Asians but not in Caucasians in the same study. Polymorphism of the SCGB3A2 gene thus may contribute to asthma risk, particularly in Asian population. The expression of SCGB3A2 was reported in human carcinomas, suggesting the use of this protein as a tumour marker. SCGB3A2 normally expressed in pulmonary club cells, was found negative in Type II cell hyperplasias and adenomas. However, it was expressed in alveolar Type II cell carcinomas and club cell adenocarcinomas. SCGB3A2 has been shown as a potentially useful marker for diagnosis of pulmonary tumours both in mice and humans.

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