Disease relevance of Sftpb

• Ablation of the SP-B gene disrupts the routing, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth [1].
• Modest overexpression of TTF-1 caused type II cell hyperplasia and increased the cellular content of SP-B [2].
• Lung hemorrhage was coincident with disruption of the mesenchymal-epithelial cell interfaces in the alveolar and bronchiolar regions of the lung parenchyma and was associated with increased apoptosis and reduced surfactant protein B (SP-B) expression [3].
• Recruitment of inflammatory cells and elaboration of proinflammatory cytokines in bronchoalveolar lavage fluid were reduced in SP-B-overexpressing mice compared with SP-B(+/-) mice, suggesting that SP-B inhibited endotoxin-induced lung inflammation [4].
• The larger decrease in lung compliance in SP-B(+/-) mice was associated with increased severity of pulmonary edema, hemorrhage and inflammation, lung permeability and protein leakage into the alveolar space [5].

High impact information on Sftpb

• Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space [6].
• Mice with a single mutated SP-B allele (+/-) were unaffected, whereas homozygous SP-B -/- offspring died of respiratory failure immediately after birth [1].
• SP-B protein and mRNA were undetectable and tubular myelin figures were lacking in SP-B -/- mice [1].
• To further assess the role of SP-B in lung function, the SP-B gene was disrupted by homologous recombination in murine mouse embryonic stem cells [1].
• Point mutations of these binding sites eliminated factor binding and resulted in significant decreases in transfected SPB promoter activity [7].

Chemical compound and disease context of Sftpb

• Doxycycline-regulated expression of SP-B fully corrected lung function in compound SP-B-/- mice and protected mice from respiratory failure at birth [8].
• Neonates with clinical SP-B deficiency best demonstrate the key role of SP-B in surfactant function. "Classic" deficiency results in severe respiratory failure in term infants and death unless lung transplantation is performed [9].

Biological context of Sftpb

• In a previous study, we showed that the SPB promoter specifically activated expression of a linked reporter gene in the continuous H441 lung cell line and that H441 nuclear proteins specifically protected a region of this promoter from bp -111 to -73 [7].
• Using reciprocal bone marrow transplantation (BMT) to generate HO-1-chimeric mice, we found that absence of HO-1 in the lung parenchyma, not in bone marrow-derived inflammatory cells, was responsible for enhanced SP-B downregulation and severe physiologic lung dysfunction [10].
• Despite normal survival, pulmonary function studies demonstrated a consistent decrease in lung compliance in SP-B(+/-) mice [11].
• Surfactant protein-B (SP-B) is a small, hydrophobic peptide that plays a critical role in pulmonary function and surfactant homeostasis [5].
• Residual volumes were increased in the SP-B(+/-) mice [11].

Anatomical context of Sftpb

• From gestational Day 17 and thereafter, pro- SP-B was detectable in Type II cells and bronchiolar epithelial cells, whereas pro-SP-C was restricted to Type II cells [12].
• Intratracheal murine TNF-alpha also resulted in decreased SP-B and SP-C mRNA levels in the bronchiolar and alveolar epithelium of adult FVB/N mice, as demonstrated by S1 nuclease protection and in situ hybridization assays, despite minimal histological inflammation [13].
• Clara cell pathophysiology was evident from decreased cytoplasmic CCSP and SP-B protein levels, enlargement and disorganization of the Golgi complex, and formation of aberrant vesicular structures [14].
• In wild-type and SP-B +/- mice, small lamellar bodies with loosely organized lamellae and distinct limiting membranes were first detected on day 16 to 16.5 of gestation [15].
• The 5' flanking region of the murine SP-B contains cell-specific cis-active elements that regulate SP-B expression in the respiratory epithelium [16].

Associations of Sftpb with chemical compounds

• Withdrawal from doxycycline caused rapid regression of the tumors associated with rapid loss of the differentiation markers TTF-1, SP-B, and proSP-C [17].
• However, a dramatic reduction in surfactant protein-B (SP-B) expression was observed in the lungs of LPS-treated HO-1(-/-) mice compared with similarly treated WT mice [10].
• SP-B is synthesized in alveolar type II cells as a preproprotein and processed to the mature peptide by the cleavage of NH2- and COOH-terminal peptides [18].
• Although specific lung compliance in room air in SP-B(+/-) mice was slightly reduced as compared with that in SP-B(+/+) mice, it was reduced more markedly during hyperoxia (46% versus 25% decrease, respectively) [5].
• Meanwhile, HIMF increased transcription activity and prevented actinomycin D-facilitated SP-B and SP-C mRNA degradation in MLE-12 cells [19].

Physical interactions of Sftpb

• Point mutation of the distal AP-1 binding site partially blocked c-Jun-mediated inhibition of the SP-B promoter [20].

Regulatory relationships of Sftpb

• Genetically decreased levels of SP-B combined with superimposed O(2)-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo [21].

Other interactions of Sftpb

• In normal mouse lung, the messenger RNAs (mRNAs) for SP-A, SP-B, and SP-D were expressed in both type II cells and Clara cells [22].
• Pro-SP-B and pro-SP-C were first detected on gestational Day 11, being localized to the cytoplasm of airway epithelial cells [12].
• Transgenic mice expressing TGF-alpha were rescued from NiSO4 injury (that is, they had diminished SP-B loss and increased survival time) [23].
• FGF signaling is required for maintenance of surfactant homeostasis and lung function during hyperoxia in vivo, mediated, at least in part, by its role in the maintenance of SP-B expression [24].
• Regulation of mouse SP-B gene promoter by AP-1 family members [20].

Analytical, diagnostic and therapeutic context of Sftpb

• The temporal-spatial expression of HIMF, SP-B, and SP-C in developing mouse lungs was examined by immunohistochemical staining, Western blot, and RT-PCR [19].
• Tissue specificity and developmental expression of SP-B mRNA was assessed by Northern blot analysis [25].
• Collectively, these results demonstrate a role for the C-terminal propeptide of SP-B in SP-C proprotein processing and the maintenance of lamellar body size [26].
• Lung lavage fluid was evaluated biochemically and for the presence of surfactant protein A (SP-A) and B (SP-B) by enzyme-linked immunosorbent assay and Western blot [27].
• By immunofluorescence, proSP-C was aggregated within alveolar Type II cells in a compartment separate from SP-B [28].

References