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Gene Review

Sftpb  -  surfactant associated protein B

Mus musculus

Synonyms: AI562151, Pulmonary surfactant-associated protein B, Pulmonary surfactant-associated proteolipid SPL(Phe), SF-B, SP-B, ...
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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


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


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


  1. Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Clark, J.C., Wert, S.E., Bachurski, C.J., Stahlman, M.T., Stripp, B.R., Weaver, T.E., Whitsett, J.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  2. Increased expression of thyroid transcription factor-1 (TTF-1) in respiratory epithelial cells inhibits alveolarization and causes pulmonary inflammation. Wert, S.E., Dey, C.R., Blair, P.A., Kimura, S., Whitsett, J.A. Dev. Biol. (2002) [Pubmed]
  3. Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor. Kalinichenko, V.V., Lim, L., Stolz, D.B., Shin, B., Rausa, F.M., Clark, J., Whitsett, J.A., Watkins, S.C., Costa, R.H. Dev. Biol. (2001) [Pubmed]
  4. Surfactant protein B inhibits endotoxin-induced lung inflammation. Epaud, R., Ikegami, M., Whitsett, J.A., Jobe, A.H., Weaver, T.E., Akinbi, H.T. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  5. Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury. Tokieda, K., Iwamoto, H.S., Bachurski, C., Wert, S.E., Hull, W.M., Ikeda, K., Whitsett, J.A. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  6. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Botas, C., Poulain, F., Akiyama, J., Brown, C., Allen, L., Goerke, J., Clements, J., Carlson, E., Gillespie, A.M., Epstein, C., Hawgood, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis. Bohinski, R.J., Di Lauro, R., Whitsett, J.A. Mol. Cell. Biol. (1994) [Pubmed]
  8. SP-B deficiency causes respiratory failure in adult mice. Melton, K.R., Nesslein, L.L., Ikegami, M., Tichelaar, J.W., Clark, J.C., Whitsett, J.A., Weaver, T.E. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  9. Surfactant protein B deficiency: insights into surfactant function through clinical surfactant protein deficiency. Thompson, M.W. Am. J. Med. Sci. (2001) [Pubmed]
  10. Absence of heme oxygenase-1 expression in the lung parenchyma exacerbates endotoxin-induced acute lung injury and decreases surfactant protein-B levels. Fredenburgh, L.E., Baron, R.M., Carvajal, I.M., Mouded, M., Macias, A.A., Ith, B., Perrella, M.A. Cell. Mol. Biol. (Noisy-le-grand) (2005) [Pubmed]
  11. Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice. Clark, J.C., Weaver, T.E., Iwamoto, H.S., Ikegami, M., Jobe, A.H., Hull, W.M., Whitsett, J.A. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  12. Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung. Zhou, L., Lim, L., Costa, R.H., Whitsett, J.A. J. Histochem. Cytochem. (1996) [Pubmed]
  13. Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung. Pryhuber, G.S., Bachurski, C., Hirsch, R., Bacon, A., Whitsett, J.A. Am. J. Physiol. (1996) [Pubmed]
  14. l7Rn6 encodes a novel protein required for clara cell function in mouse lung development. Fernández-Valdivia, R., Zhang, Y., Pai, S., Metzker, M.L., Schumacher, A. Genetics (2006) [Pubmed]
  15. Lamellar body formation in normal and surfactant protein B-deficient fetal mice. Stahlman, M.T., Gray, M.P., Falconieri, M.W., Whitsett, J.A., Weaver, T.E. Lab. Invest. (2000) [Pubmed]
  16. Structure and function of the mouse surfactant protein B gene. Bruno, M.A., Bohinski, R.J., Carter, J.E., Foss, K.A., Whitsett, J.A. Am. J. Physiol. (1995) [Pubmed]
  17. FGF-10 disrupts lung morphogenesis and causes pulmonary adenomas in vivo. Clark, J.C., Tichelaar, J.W., Wert, S.E., Itoh, N., Perl, A.K., Stahlman, M.T., Whitsett, J.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  18. Processing of pulmonary surfactant protein B by napsin and cathepsin H. Ueno, T., Linder, S., Na, C.L., Rice, W.R., Johansson, J., Weaver, T.E. J. Biol. Chem. (2004) [Pubmed]
  19. Hypoxia-induced mitogenic factor modulates surfactant protein B and C expression in mouse lung. Tong, Q., Zheng, L., Dodd-o, J., Langer, J., Wang, D., Li, D. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  20. Regulation of mouse SP-B gene promoter by AP-1 family members. Sever-Chroneos, Z., Bachurski, C.J., Yan, C., Whitsett, J.A. Am. J. Physiol. (1999) [Pubmed]
  21. Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury. Ikegami, M., Weaver, T.E., Conkright, J.J., Sly, P.D., Ross, G.F., Whitsett, J.A., Glasser, S.W. J. Appl. Physiol. (2002) [Pubmed]
  22. Surfactant protein C expression in urethane-induced murine pulmonary tumors. Mason, R.J., Kalina, M., Nielsen, L.D., Malkinson, A.M., Shannon, J.M. Am. J. Pathol. (2000) [Pubmed]
  23. Pathogenomic mechanisms for particulate matter induction of acute lung injury and inflammation in mice. Leikauf, G.D., McDowell, S.A., Wesselkamper, S.C., Miller, C.R., Hardie, W.D., Gammon, K., Biswas, P.P., Korfhagen, T.R., Bachurski, C.J., Wiest, J.S., Willeke, K., Bingham, E., Leikauf, J.E., Aronow, B.J., Prows, D.R. Research report (Health Effects Institute) (2001) [Pubmed]
  24. FGF signaling is required for pulmonary homeostasis following hyperoxia. Hokuto, I., Perl, A.K., Whitsett, J.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  25. Sequence, ontogeny, and cellular localization of murine surfactant protein B mRNA. D'Amore-Bruno, M.A., Wikenheiser, K.A., Carter, J.E., Clark, J.C., Whitsett, J.A. Am. J. Physiol. (1992) [Pubmed]
  26. Rescue of SP-B knockout mice with a truncated SP-B proprotein. Function of the C-terminal propeptide. Akinbi, H.T., Breslin, J.S., Ikegami, M., Iwamoto, H.S., Clark, J.C., Whitsett, J.A., Jobe, A.H., Weaver, T.E. J. Biol. Chem. (1997) [Pubmed]
  27. Pulmonary alveolar proteinosis in SCID mice. Jennings, V.M., Dillehay, D.L., Webb, S.K., Brown, L.A. Am. J. Respir. Cell Mol. Biol. (1995) [Pubmed]
  28. Progressive lung disease and surfactant dysfunction with a deletion in surfactant protein C gene. Hamvas, A., Nogee, L.M., White, F.V., Schuler, P., Hackett, B.P., Huddleston, C.B., Mendeloff, E.N., Hsu, F.F., Wert, S.E., Gonzales, L.W., Beers, M.F., Ballard, P.L. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
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