Genomes and Genes
Gene Symbol: Sftpc
Description: surfactant associated protein C
Alias: Bricd6, SP-C, SP5, SPC, Sftp-2, Sftp2, pro-SpC, pulmonary surfactant-associated protein C, pulmonary surfactant-associated proteolipid SPL(Val)
- Tsao P, Vasconcelos M, Izvolsky K, Qian J, LU J, Cardoso W. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development. 2009;136:2297-307 pubmed publisher..It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease. ..
- Bachurski C, Yang G, Currier T, Gronostajski R, Hong D. Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. Mol Cell Biol. 2003;23:9014-24 pubmedSurfactant protein C (SP-C; Sftpc) gene expression is restricted to pulmonary type II epithelial cells...
- Wan H, Dingle S, Xu Y, Besnard V, Kaestner K, Ang S, et al. Compensatory roles of Foxa1 and Foxa2 during lung morphogenesis. J Biol Chem. 2005;280:13809-16 pubmed..Foxa family members regulate signaling and transcriptional programs required for morphogenesis and cell differentiation during formation of the lung. ..
- Yang H, Lu M, Zhang L, Whitsett J, Morrisey E. GATA6 regulates differentiation of distal lung epithelium. Development. 2002;129:2233-46 pubmed..Together, these data implicate GATA6 as an important regulator of distal epithelial cell differentiation and proximal airway development in the mouse. ..
- Jin N, Cho S, Raso M, Wistuba I, Smith Y, Yang Y, et al. Mig-6 is required for appropriate lung development and to ensure normal adult lung homeostasis. Development. 2009;136:3347-56 pubmed publisher..These results demonstrate that Mig-6 is required for prenatal and perinatal lung development, in part through the regulation of EGF signaling, as well as for maintaining proper pulmonary vascularization. ..
- Bird A, Flecknoe S, Tan K, Olsson P, Antony N, Mantamadiotis T, et al. cAMP response element binding protein is required for differentiation of respiratory epithelium during murine development. PLoS ONE. 2011;6:e17843 pubmed publisher..Together, these results demonstrate a crucial role for Creb1 activity for the development and differentiation of the conducting and distal lung epithelium. ..
- Arora R, Metzger R, Papaioannou V. Multiple roles and interactions of Tbx4 and Tbx5 in development of the respiratory system. PLoS Genet. 2012;8:e1002866 pubmed publisher..Finally, we show that Tbx4 and Tbx5 interact with Fgf10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development. ..
- Cole T, Blendy J, Monaghan A, Krieglstein K, Schmid W, Aguzzi A, et al. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 1995;9:1608-21 pubmed
- Desai T, Brownfield D, Krasnow M. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature. 2014;507:190-4 pubmed publisher..We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate. ..
- Guseh J, Bores S, Stanger B, Zhou Q, Anderson W, Melton D, et al. Notch signaling promotes airway mucous metaplasia and inhibits alveolar development. Development. 2009;136:1751-9 pubmed publisher..Occasional distal cystic cells appeared to differentiate into normal proximal airway cells, suggesting that ectopic Notch signaling arrests the normal differentiation of distal lung progenitors before they initiate an alveolar program. ..
- Geng Y, Dong Y, Yu M, Zhang L, Yan X, Sun J, et al. Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development. Proc Natl Acad Sci U S A. 2011;108:7058-63 pubmed publisher..Therefore, we provide in vivo and in vitro evidence to demonstrate that Fstl1 modulates lung development and alveolar maturation, in part, through BMP4 signaling...
- Minoo P, Hu L, Xing Y, Zhu N, Chen H, Li M, et al. Physical and functional interactions between homeodomain NKX2.1 and winged helix/forkhead FOXA1 in lung epithelial cells. Mol Cell Biol. 2007;27:2155-65 pubmed..winged-helix/forkhead family of FOXA transcription factors to regulate two spatially and cell type-specific genes, SpC and Ccsp. The results show that NKX2.1 interacts physically and functionally with FOXA1...
- Barkauskas C, Cronce M, Rackley C, Bowie E, Keene D, Stripp B, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest. 2013;123:3025-36 pubmed publisher..Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-..
- Quaggin S, Schwartz L, Cui S, Igarashi P, Deimling J, Post M, et al. The basic-helix-loop-helix protein pod1 is critically important for kidney and lung organogenesis. Development. 1999;126:5771-83 pubmed..Defects specific to later specialized cell types where Pod1 is expressed, such as the podocytes, were also observed, suggesting that this transcription factor may play multiple roles in kidney morphogenesis. ..
- Glasser S, Witt T, Senft A, Baatz J, Folger D, Maxfield M, et al. Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol. 2009;297:L64-72 pubmed publisher..more severe interstitial thickening, air space consolidation, and goblet cell hyperplasia in SP-C-deficient (Sftpc(-/-)) mice compared with SP-C replete mice...
- Chapman H, Li X, Alexander J, Brumwell A, Lorizio W, Tan K, et al. Integrin ?6?4 identifies an adult distal lung epithelial population with regenerative potential in mice. J Clin Invest. 2011;121:2855-62 pubmed publisher..mouse alveolar epithelial cells (AECs) expressing the laminin receptor ?6?4, but little or no pro-surfactant C (pro-SPC), is endowed with regenerative potential...
- Metzger D, Stahlman M, Shannon J. Misexpression of ELF5 disrupts lung branching and inhibits epithelial differentiation. Dev Biol. 2008;320:149-60 pubmed publisher..inducible HA-tagged mouse Elf5 transgene was placed under the control of the lung epithelium-specific human SFTPC promoter...
- Zhao J, Chen H, Peschon J, Shi W, Zhang Y, Frank S, et al. Pulmonary hypoplasia in mice lacking tumor necrosis factor-alpha converting enzyme indicates an indispensable role for cell surface protein shedding during embryonic lung branching morphogenesis. Dev Biol. 2001;232:204-18 pubmed
- Ramasamy S, Mailleux A, Gupte V, Mata F, Sala F, Veltmaat J, et al. Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development. Dev Biol. 2007;307:237-47 pubmed..Thus, our results indicate that FGF10 plays a pivotal role in maintaining epithelial progenitor cell proliferation as well as coordinating alveolar smooth muscle cell formation and vascular development. ..
- Metzger D, Xu Y, Shannon J. Elf5 is an epithelium-specific, fibroblast growth factor-sensitive transcription factor in the embryonic lung. Dev Dyn. 2007;236:1175-92 pubmed..5 lungs. These results demonstrate that Elf5 is an FGF-sensitive transcription factor in the lung with a dynamic pattern of expression and that FGF regulation of Elf5 by means of FGFR2b occurs through the PI3-Kinase/Akt pathway. ..
- Grad I, McKee T, Ludwig S, Hoyle G, Ruiz P, Wurst W, et al. The Hsp90 cochaperone p23 is essential for perinatal survival. Mol Cell Biol. 2006;26:8976-83 pubmed..Thus, p23 contributes a nonredundant, temporally restricted, and tissue-specific function during mouse development. ..
- Zhou L, Lim L, Costa R, Whitsett J. Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung. J Histochem Cytochem. 1996;44:1183-93 pubmed..The early expression of TTF-1 and HNF-3beta, preceding and overlapping that of pro-SP-B, mature SP-B, pro-SP-C, and CCSP, supports a regulatory role for TTF-1 and HNF-3beta in lung-specific gene expression. ..
- DeFelice M, Silberschmidt D, DiLauro R, Xu Y, Wert S, Weaver T, et al. TTF-1 phosphorylation is required for peripheral lung morphogenesis, perinatal survival, and tissue-specific gene expression. J Biol Chem. 2003;278:35574-83 pubmed..Direct and indirect transcriptional targets of TTF-1 were identified that are likely to play important roles in lung formation and function. ..
- Klinger S, Turgeon B, Lévesque K, Wood G, Aagaard Tillery K, Meloche S. Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality. Proc Natl Acad Sci U S A. 2009;106:16710-5 pubmed publisher..Our findings reveal a critical role for Erk3 in the establishment of fetal growth potential and pulmonary function in the mouse. ..
- Rawlins E, Clark C, Xue Y, Hogan B. The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development. 2009;136:3741-5 pubmed publisher..Taken together, this evidence supports a model in which the distal tip of the developing lung contains a multipotent epithelial population, the fate of which changes during development. ..
- Weaver M, Yingling J, Dunn N, Bellusci S, Hogan B. Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development. Development. 1999;126:4005-15 pubmed..Endodermal cells at the periphery of the lung, which are exposed to high levels of Bmp4, maintain or adopt a distal character, while cells receiving little or no Bmp4 signal initiate a proximal differentiation program. ..
- Minoo P, Su G, Drum H, Bringas P, Kimura S. Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos. Dev Biol. 1999;209:60-71 pubmed..These results demonstrate a critical role for Nkx2.1 in morphogenesis of the anterior foregut and the lung as well as in differentiation of pulmonary epithelial cells. ..
- Rock J, Barkauskas C, Cronce M, Xue Y, Harris J, Liang J, et al. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci U S A. 2011;108:E1475-83 pubmed publisher..Taken together, our results show a previously unappreciated heterogeneity of cell types proliferating in fibrotic lesions and exclude pericytes and two epithelial cell populations as the origin of myofibroblasts...
- Okubo T, Hogan B. Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. J Biol. 2004;3:11 pubmed..We discuss the relevance of our findings to the poorly understood pathological condition of intestinal metaplasia in humans. ..
- Glasser S, Senft A, Whitsett J, Maxfield M, Ross G, Richardson T, et al. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice. J Immunol. 2008;181:621-8 pubmedTo determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection...
- Bridges J, Ikegami M, Brilli L, Chen X, Mason R, Shannon J. LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. J Clin Invest. 2010;120:1736-48 pubmed publisher..Collectively, these data demonstrate that full LPCAT1 activity is required to achieve the levels of SatPC essential for the transition to air breathing. ..
- Gründer A, Ebel T, Mallo M, Schwarzkopf G, Shimizu T, Sippel A, et al. Nuclear factor I-B (Nfib) deficient mice have severe lung hypoplasia. Mech Dev. 2002;112:69-77 pubmed..Our study demonstrates that Nfib is essential for normal lung development, and suggests that it could be involved in the pathogenesis of respiratory distress syndromes in humans. ..
- Wan H, Luo F, Wert S, Zhang L, Xu Y, Ikegami M, et al. Kruppel-like factor 5 is required for perinatal lung morphogenesis and function. Development. 2008;135:2563-72 pubmed publisher..KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth. ..
- Reynolds S, Zemke A, Giangreco A, Brockway B, Teisanu R, Drake J, et al. Conditional stabilization of beta-catenin expands the pool of lung stem cells. Stem Cells. 2008;26:1337-46 pubmed publisher..Our data demonstrate that the differentiation-modulating activities of stabilized beta-catenin account for expansion of tissue stem cells. ..
- Yamamoto H, Yun E, Gerber H, Ferrara N, Whitsett J, Vu T. Epithelial-vascular cross talk mediated by VEGF-A and HGF signaling directs primary septae formation during distal lung morphogenesis. Dev Biol. 2007;308:44-53 pubmed
- Bellusci S, Furuta Y, Rush M, Henderson R, Winnier G, Hogan B. Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development. 1997;124:53-63 pubmed..By contrast, Ptc is clearly upregulated in the transgenic lung. These results thus establish a role for SHH in lung morphogenesis, and suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo. ..
- Moreno Barriuso N, López Malpartida A, de Pablo F, Pichel J. Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF-I double deficient embryos. Dev Dyn. 2006;235:2040-50 pubmed..The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF-I in lung alveolar epithelium and vascular maturation. ..
- Okubo T, Knoepfler P, Eisenman R, Hogan B. Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation. Development. 2005;132:1363-74 pubmed..Overexpression of NmycEGFP in the epithelium under the control of surfactant protein C (Sftpc) regulatory elements expands the domain of S phase cells and upregulates numerous genes associated with growth and ..
- Xu X, Rock J, Lu Y, Futtner C, Schwab B, Guinney J, et al. Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma. Proc Natl Acad Sci U S A. 2012;109:4910-5 pubmed publisher..quot;knock-in" Cre-estrogen receptor alleles to inducibly express K-RasG12D in CC10(+) epithelial cells and Sftpc(+) type II alveolar cells of the adult mouse lung...
- Liu Y, Jiang H, Crawford H, Hogan B. Role for ETS domain transcription factors Pea3/Erm in mouse lung development. Dev Biol. 2003;261:10-24 pubmed..Our results provide the first functional evidence that Pea3 subfamily members play a role in epithelial-mesenchymal interactions during lung organogenesis. ..
- D Amore Bruno M, Wikenheiser K, Carter J, Clark J, Whitsett J. Sequence, ontogeny, and cellular localization of murine surfactant protein B mRNA. Am J Physiol. 1992;262:L40-7 pubmed..The murine SP-B mRNA was expressed in proximal and distal epithelial cells within the respiratory tract and shares a close structural relationship to SP-B from other species...
- Shu W, Guttentag S, Wang Z, Andl T, Ballard P, Lu M, et al. Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung. Dev Biol. 2005;283:226-39 pubmed..Thus, Wnt/beta-catenin signaling is a critical upstream regulator of proximal-distal patterning in the lung, in part, through regulation of N-myc, BMP4, and FGF signaling. ..
- Goss A, Tian Y, Tsukiyama T, Cohen E, Zhou D, Lu M, et al. Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut. Dev Cell. 2009;17:290-8 pubmed publisher..Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut...
- Koutsourakis M, Keijzer R, Visser P, Post M, Tibboel D, Grosveld F. Branching and differentiation defects in pulmonary epithelium with elevated Gata6 expression. Mech Dev. 2001;105:105-14 pubmed..Thus, elevated levels of GATA6 protein affect early lung development and in analogy to other GATA factors in other tissues, GATA6 also plays a crucial role in the terminal differentiation in this case of the distal pulmonary epithelium. ..
- Sylva M, Li V, Buffing A, van Es J, van den Born M, van der Velden S, et al. The BMP antagonist follistatin-like 1 is required for skeletal and lung organogenesis. PLoS ONE. 2011;6:e22616 pubmed publisher..Taken together, these observations show that Fstl1 is a crucial regulator in BMP signalling during mouse development. ..
- Roos A, Berg T, Barton J, Didon L, Nord M. Airway epithelial cell differentiation during lung organogenesis requires C/EBP? and C/EBP?. Dev Dyn. 2012;241:911-23 pubmed publisher..Epithelial differentiation was assessed in mice with a lung epithelial-specific (SFTPC-Cre-mediated) deletion of C/EBP? (Cebpa(?LE) ), C/EBP? (Cebpb(?LE) ), or both genes (Cebpa(?LE) ; Cebpb(?LE) )...
- Lin S, Ikegami M, Xu Y, Bosserhoff A, Malkinson A, Shannon J. Misexpression of MIA disrupts lung morphogenesis and causes neonatal death. Dev Biol. 2008;316:441-55 pubmed publisher..exogenous MIA caused significant reductions in the expression of the lung differentiation markers Sftpa, Sftpb, Sftpc, and Abca3. Bitransgenic mice expressing MIA under the control of the SFTPC promoter after E16...
- Volckaert T, Campbell A, Dill E, Li C, Minoo P, De Langhe S. Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors. Development. 2013;140:3731-42 pubmed publisher..Interestingly, our data presented here show that once epithelial cells are committed to the Sox2-positive airway epithelial cell fate, Fgf10 prevents ciliated cell differentiation and promotes basal cell differentiation. ..
- O Brien K, Alberich Jorda M, Yadav N, Kocher O, Diruscio A, Ebralidze A, et al. CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells. Development. 2010;137:2147-56 pubmed publisher..These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells. ..
- Zhang Y, Goss A, Cohen E, Kadzik R, Lepore J, Muthukumaraswamy K, et al. A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nat Genet. 2008;40:862-70 pubmed publisher..Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration. ..
- Glasser S, Detmer E, Ikegami M, Na C, Stahlman M, Whitsett J. Pneumonitis and emphysema in sp-C gene targeted mice. J Biol Chem. 2003;278:14291-8 pubmed..Absence of SP-C caused a severe progressive pulmonary disorder with histologic features consistent with interstitial pneumonitis. ..
- Wan H, Xu Y, Ikegami M, Stahlman M, Kaestner K, Ang S, et al. Foxa2 is required for transition to air breathing at birth. Proc Natl Acad Sci U S A. 2004;101:14449-54 pubmed..Foxa2 regulates a complex pulmonary program of epithelial cell maturation required for transition to air breathing at birth. ..
- Tiozzo C, De Langhe S, Yu M, Londhe V, Carraro G, Li M, et al. Deletion of Pten expands lung epithelial progenitor pools and confers resistance to airway injury. Am J Respir Crit Care Med. 2009;180:701-12 pubmed publisher..composed of basal cells in the trachea, CGRP/CC10 double-positive neuroendocrine cells in the bronchi, and CC10/SPC double-positive cells at the bronchioalveolar duct junctions...
- Glasser S, Burhans M, Korfhagen T, Na C, Sly P, Ross G, et al. Altered stability of pulmonary surfactant in SP-C-deficient mice. Proc Natl Acad Sci U S A. 2001;98:6366-71 pubmed
- Li A, Hardy R, Stoner S, Tuckermann J, Seibel M, Zhou H. Deletion of mesenchymal glucocorticoid receptor attenuates embryonic lung development and abdominal wall closure. PLoS ONE. 2013;8:e63578 pubmed publisher..In addition, altered glucocorticoid signaling in the mesenchyme attenuates normal lung epithelial differentiation...