Disease relevance of Scgb1a1

• In transient expression assays, CC10 sequences were capable of restricting CAT expression to a human lung adenocarcinoma cell line similar to pulmonary Clara cells [1].
• Results reported here reveal that the acute inhalation of a commercial insecticide produces hypertrophy of Clara cells, a significant augmentation of CC10 synthesis, and probably differentiation de novo of Clara cells, and morphological changes compatible with a detoxification process [2].
• Surfactant protein and CC-10 expression in acute lung injury and in response to keratinocyte growth factor [3].
• Here we explore the hypothesis that CCSP-positive Clara cells are highly responsive to AhR ligands and are the primary cell type involved in BaP- and TCDD-induced toxicities [4].
• The aim of this study was to investigate the expression of CCSP in endotoxin-induced otitis media with effusion (OME) in the rat [5].

High impact information on Scgb1a1

• CCSP gene expression is an informative developmental marker within the bronchiolar epithelium recapitulating cellular differentiation in the distal respiratory epithelium during late fetal and early postnatal life [6].
• To define the mechanisms that establish and maintain gene expression within this epithelium, CCSP-human growth hormone chimeric gene constructs were created and used to generate transgenic mice [6].
• Clara cell secretory protein (CCSP) is an abundant 10-kDa protein synthesized and secreted by nonciliated epithelial cells lining the respiratory and terminal bronchioles of the lung [6].
• RNA blot analysis of organs from F1 transgenic offspring and normal littermates revealed that cis-acting elements within 2.25 kilobases of the 5' flanking region of the CCSP gene were sufficient to direct lung-specific expression of human growth hormone [6].
• In situ hybridization and immunohistochemistry of individual bronchioles revealed that human growth hormone expression in the respiratory epithelium of these mice was confined to Clara cells, consistent with observations of the endogenous CCSP gene [6].

Biological context of Scgb1a1

• Interestingly, DNA sequence analysis and prediction of the amino acid sequence reveals that the PCB-binding protein shares 53% positional amino acid identity with uteroglobin, a progesterone-binding protein found in rabbit uterus and lung [7].
• The amino acid sequence of rat Clara Cell 10 kDa secretory protein (CC10) shows 55% identity to rabbit uteroglobin [8].
• METHODS: We studied the mRNA expression of surfactant proteins (SP) A, -B, -C and -D and Clara cell secretory protein (CC10) with RT-PCR and in situ hybridization and protein expression of CC10, SP-A and -D with immunohistochemistry in the lungs of a preterm rat model, in which experimental BPD was induced by prolonged oxidative stress [9].
• The interactions of nuclear proteins with a particular segment of the CC10 promoter which extends from 79 to 128 bp upstream of the CC10 transcription initiation site (CC10 region I) have now been studied [10].
• Transcripts for the CAT reporter gene colocalized with those for the endogenous murine CC10 gene within the airways of transgenic mice [1].

Anatomical context of Scgb1a1

• Intratracheal instillation of IL-13 induced CCSP mRNA in epithelial cells without cilia within 8-16 h, maximal between 24 and 48 h; CCSP immunostaining increased in a time-dependent fashion, maximal at 48 h [11].
• The CCSP immunostaining was localized in nongranulated secretory cells and goblet cells and in the lumen [11].
• Pretreatment with the selective EGFR tyrosine kinase inhibitor BIBX1522, cyclophosphamide (an inhibitor of bone marrow leukocyte mobilization), or a blocking antibody to IL-8 prevented CCSP staining [11].
• The identity of the PCB-binding protein is supported by expression of the cDNA in Cos-1 cells where the homogenates from transfected cells show specific binding of 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, a high affinity ligand for the PCB-binding protein [7].
• We report that like rabbit uteroglobin, rat CC10 mRNA is expressed in lung and esophagus, as well as in uteri of estrogen- and progesterone-treated females [8].

Associations of Scgb1a1 with chemical compounds

• Selective EGFR tyrosine kinase inhibitors, BIBX1522 and AG1478, prevented CCSP expression in NCI-H292 cells, but the platelet-derived growth factor receptor tyrosine kinase inhibitor AG1295 had no effect [11].
• Except for SP-A, the cellular distribution of SP-B, -C, -D and CC10, studied with in situ hybridization and/or immunohistochemistry, did not change in room air nor in hyperoxia [9].
• However, administration of pilocarpine abolishes this difference in CC10 abundance [12].
• Previous studies have identified a number of proteins which bind to a functionally important region (Region 1) located -132 to -76 bp from the transcription start site in the rat CCSP gene [13].
• In utero exposure to the synthetic glucocorticoid betamethasone was shown to increase specific 4,4'-bis([3H]methylsulfonyl)2,2',5,5'- tetrachlorobiphenyl binding, PCB-BP protein, and PCB-BP mRNA if administered from gestational Day 18 and onward [14].

Regulatory relationships of Scgb1a1

• These findings indicate that IL-13 induces CCSP expression via an EGFR- and leukocyte-dependent pathway [11].

Other interactions of Scgb1a1

• Because Clara cell secretory protein (CCSP) expression has been reported in cells that express mucins, we examined the effect of IL-13 on CCSP gene and protein expression in pathogen-free rat airways and in pulmonary mucoepidermoid NCI-H292 cells [11].

Analytical, diagnostic and therapeutic context of Scgb1a1

• Furthermore, the antibodies detected significantly higher levels of the lung PCB-binding protein in lavage fluid from nonsmokers as compared to smokers [15].
• Standard immunohistochemical techniques and laser scanning confocal microscopy were used to assess changes in the abundance of Clara cell 10 kD protein (CC10) within granules and endoplasmic reticulum of rat nonciliated cells after the administration of the secretagogue pilocarpine [12].
• By western blot, CC10 immunoreactive bands strongly increased in lungs after insecticide treatment, but they were only slightly higher than the control when the vehicle of the insecticide was tested [2].
• BaP- and TCDD-induced mRNA and protein levels of CYP1A1 and CYP1B1 levels were significantly elevated in CCSP-positive cell cultures [4].
• RESULTS: RT-PCR revealed that the expression of CCSP was first identified at 1 h after endotoxin instillation, was dramatically increased between 1 h and Day 1, with maximal expression at 12 h, and then decreased after Day 3 [5].

References