Genomes and Genes
Gene Symbol: Scgb1a1
Description: secretoglobin, family 1A, member 1 (uteroglobin)
Alias: CC10, CC16, CCSP, PCB-BP, UGB, Utg, uteroglobin, Blastokinin, CCPBP, PCB-binding protein, clara cell 17 kDa protein, clara cell phospholipid-binding protein, clara cell secretory protein, clara cells 10 kDa secretory protein, secretoglobin family 1A member 1
- Mukherjee A, Kundu G, Mantile Selvaggi G, Yuan C, Mandal A, Chattopadhyay S, et al. Uteroglobin: a novel cytokine?. Cell Mol Life Sci. 1999;55:771-87 pubmedBlastokinin or uteroglobin (UG) is a steroid-inducible, evolutionarily conserved, multifunctional protein secreted by the mucosal epithelial of virtually all mammals. It is present in the blood and in other body fluids including urine...
- 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. ..
- Xing Y, Li C, Li A, Sridurongrit S, Tiozzo C, Bellusci S, et al. Signaling via Alk5 controls the ontogeny of lung Clara cells. Development. 2010;137:825-33 pubmed publisher..Thus, the signaling pathway by which TGFbeta/ALK5 regulates Clara cell differentiation may entail inhibition of Pten expression, which in turn activates ERK and AKT phosphorylation. ..
- 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..We propose a model in which Nmyc is essential in the developing lung for maintaining a distal population of undifferentiated, proliferating progenitor cells. ..
- 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. ..
- 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. ..
- Chen L, Zhang Z, Myers A, Huang S. Cutting edge: altered pulmonary eosinophilic inflammation in mice deficient for Clara cell secretory 10-kDa protein. J Immunol. 2001;167:3025-8 pubmedb>Clara cell secretory protein (CC10) is a steroid-inducible protein, and its in vivo function is currently unclear. The role of CC10 in modulation of pulmonary allergic inflammation was examined in mice deficient for the CC10 gene...
- 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. ..
- 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..Similarly, epithelial cells labeled with our Scgb1a1-CreER allele do not give rise to fibroblasts but generate both AEC2 and AEC1 cells in response to bleomycin-..
- 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..HNF-3beta), prosurfactant proteins B and C (pro-SP-B, pro-SP-C), surfactant protein B (SP-B), and Clara cell secretory protein (CCSP) in developing mouse lung...
- 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. ..
- 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. ..
- 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...
- Guha A, Vasconcelos M, Cai Y, Yoneda M, Hinds A, Qian J, et al. Neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways. Proc Natl Acad Sci U S A. 2012;109:12592-7 pubmed publisher..bodies (NEBs), distinguished by their strong Scgb3a2 and uroplakin 3a (Upk3a) signals and reduced Ccsp (Scgb1a1) expression...
- Boucherat O, Montaron S, Bérubé Simard F, Aubin J, Philippidou P, Wellik D, et al. Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis. Am J Physiol Lung Cell Mol Physiol. 2013;304:L817-30 pubmed publisher..Altogether, our observations establish that the Hoxa5 and Hoxb5 paralog genes shared some functions during lung morphogenesis, Hoxa5 playing a predominant role. ..
- 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. ..
- Shu W, Lu M, Zhang Y, Tucker P, Zhou D, Morrisey E. Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development. 2007;134:1991-2000 pubmed
- Collins B, Kleeberger W, Ball D. Notch in lung development and lung cancer. Semin Cancer Biol. 2004;14:357-64 pubmed..Non-small cell lung cancers, including adenocarcinoma, appear to actively utilize this conserved developmental pathway. Pharmacologic inhibition of the Notch pathway is a potential experimental approach to lung cancer treatment. ..
- Zhang Z, Kundu G, Yuan C, Ward J, Lee E, DeMayo F, et al. Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin. Science. 1997;276:1408-12 pubmedDespite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown...
- Tichelaar J, Wert S, Costa R, Kimura S, Whitsett J. HNF-3/forkhead homologue-4 (HFH-4) is expressed in ciliated epithelial cells in the developing mouse lung. J Histochem Cytochem. 1999;47:823-32 pubmed..Cellular sites of HFH-4 and beta-tubulin IV expression were distinct from that of Clara cell secretory protein (CCSP), which was detected in nonciliated epithelial cells in the conducting airway of the lung...
- Keijzer R, van Tuyl M, Meijers C, Post M, Tibboel D, Grosveld F, et al. The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development. Development. 2001;128:503-11 pubmed..TTF1 expression is unaltered in chimeric lungs whereas SPC and CC10 expression are attenuated in abnormally branched areas of chimeric lungs...
- 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. ..
- 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..differentiation, as indicated by lack of expression of surfactant protein B, surfactant protein C, the Clara cell secretory protein, and Foxj1, was inhibited...
- 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..Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung. ..
- 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. ..
- Morimoto M, Liu Z, Cheng H, Winters N, Bader D, Kopan R. Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate. J Cell Sci. 2010;123:213-24 pubmed publisher..These analyses suggest that the impact of gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals. ..
- Xu K, Nieuwenhuis E, Cohen B, Wang W, Canty A, Danska J, et al. Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol. 2010;298:L45-56 pubmed publisher..In sum, these results demonstrate that Lfng functions to enhance Notch signaling in myofibroblast precursor cells and thereby to coordinate differentiation and mobilization of myofibroblasts required for alveolar septation. ..
- 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. ..
- Tateossian H, Hardisty Hughes R, Morse S, Romero M, Hilton H, Dean C, et al. Regulation of TGF-beta signalling by Fbxo11, the gene mutated in the Jeff otitis media mouse mutant. Pathogenetics. 2009;2:5 pubmed publisher..The finding that Fbxo11 impacts upon TGF-beta signalling has important implications for our understanding of the underlying disease mechanisms of middle ear inflammatory disease. ..
- 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..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...
- Shaw A, Meissner A, Dowdle J, Crowley D, Magendantz M, Ouyang C, et al. Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis. Genes Dev. 2007;21:694-707 pubmed..These findings indicate that in the lung, Sprouty-2 plays a critical role in the regulation of oncogenic K-ras, and implicate counter-regulatory mechanisms in the pathogenesis of Ras-based disease. ..
- Li C, Xiao J, Hormi K, Borok Z, Minoo P. Wnt5a participates in distal lung morphogenesis. Dev Biol. 2002;248:68-81 pubmed..Absence of WNT5a activity in the mutant lungs leads to increased expression of Fgf-10, Bmp4, Shh, and its receptor Ptc, raising the possibility that WNT5a, FGF-10, BMP4, and SHH signaling pathways are functionally interactive. ..
- Hung C, Chen L, Zhang Z, Chowdhury B, Lee W, Plunkett B, et al. Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein. J Allergy Clin Immunol. 2004;114:664-70 pubmedPulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown...
- 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. ..
- Blatt E, Yan X, Wuerffel M, Hamilos D, Brody S. Forkhead transcription factor HFH-4 expression is temporally related to ciliogenesis. Am J Respir Cell Mol Biol. 1999;21:168-76 pubmed
- Londhe V, Maisonet T, Lopez B, Jeng J, Li C, Minoo P. A subset of epithelial cells with CCSP promoter activity participates in alveolar development. Am J Respir Cell Mol Biol. 2011;44:804-12 pubmed publisher..Subsets of cells expressing Clara cell secretory protein (CCSP) have been identified in both lung and bone marrow compartments, and are described as a ..
- Que J, Okubo T, Goldenring J, Nam K, Kurotani R, Morrisey E, et al. Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Development. 2007;134:2521-31 pubmed..These findings suggest that Sox2 plays a second role in establishing the boundary between the keratinized, squamous esophagus/forestomach and glandular hindstomach. ..
- Mucenski M, Wert S, Nation J, Loudy D, Huelsken J, Birchmeier W, et al. beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis. J Biol Chem. 2003;278:40231-8 pubmed..These observations establish, for the first time, both the sites and timing of specification of the proximal and peripheral airways in the developing lung, and that beta-catenin is one of the essential components of this specification. ..
- Reynolds P, Mucenski M, Whitsett J. Thyroid transcription factor (TTF) -1 regulates the expression of midkine (MK) during lung morphogenesis. Dev Dyn. 2003;227:227-37 pubmed..0, MK was restricted to subsets of cells by E18.5, colocalizing with the Clara cell secretory protein (CCSP) marker in conducting airways and with pro-SPC, a marker specific for alveolar type II ..
- 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. ..
- Rawlins E, Okubo T, Xue Y, Brass D, Auten R, Hasegawa H, et al. The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell. 2009;4:525-34 pubmed publisherTo directly test the contribution of Scgb1a1(+) Clara cells to postnatal growth, homeostasis, and repair of lung epithelium, we generated a Scgb1a1-CreER "knockin" mouse for lineage-tracing these cells...
- Zeng X, Gray M, Stahlman M, Whitsett J. TGF-beta1 perturbs vascular development and inhibits epithelial differentiation in fetal lung in vivo. Dev Dyn. 2001;221:289-301 pubmed..pseudoglandular stage of development, inhibiting synthesis of differentiation-dependent proteins, SP-B, SP-C, and CCSP, and maintaining embryonic patterns of staining for thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear ..
- 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..including the proximally expressed hepatocyte nuclear factor/forkhead homologue 4 (Hfh4) and Clara cell marker CC10, and the distal marker Sp-C...
- Wuenschell C, Sunday M, Singh G, Minoo P, Slavkin H, Warburton D. Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages. J Histochem Cytochem. 1996;44:113-23 pubmed..to study expression in developing mouse lung of calcitonin gene-related peptide (CGRP), Clara cell 10-KD protein (CC10), and surfactant protein-A (SP-A), markers that are differentially expressed in neuroendocrine cells, Clara cells, ..
- Calvo F, Fillet M, de Seny D, Meuwis M, Maree R, Crahay C, et al. Biomarker discovery in asthma-related inflammation and remodeling. Proteomics. 2009;9:2163-70 pubmed publisher..We report the identification of different five proteins: found inflammatory zone 1 or RELM alpha (FIZZ-1), calcyclin (S100A6), clara cell secretory protein 10 (CC10), Ubiquitin, and Histone H4.
- Shikama N, Lutz W, Kretzschmar R, Sauter N, Roth J, Marino S, et al. Essential function of p300 acetyltransferase activity in heart, lung and small intestine formation. EMBO J. 2003;22:5175-85 pubmed..Unexpectedly, the p300 AT-mutant cells upregulate BMP-inducible genes to levels similar or even higher than observed in wild-type cells. ..
- Margraf L, Finegold M, Stanley L, Major A, Hawkins H, DeMayo F. Cloning and tissue-specific expression of the cDNA for the mouse Clara cell 10 kD protein: comparison of endogenous expression to rabbit uteroglobin promoter-driven transgene expression. Am J Respir Cell Mol Biol. 1993;9:231-8 pubmedb>Uteroglobin (UG) is a hormonally regulated secretory protein produced in the lung and urogenital system of rabbits...
- Snyder J, Reynolds S, Hollingsworth J, Li Z, Kaminski N, Stripp B. Clara cells attenuate the inflammatory response through regulation of macrophage behavior. Am J Respir Cell Mol Biol. 2010;42:161-71 pubmed publisher..Reduced Clara cell secretory function and corresponding decreases in the abundance of the major Clara cell secretory protein (CCSP) are characteristically seen in these disease states...
- Zhang D, Huang Z, Jiang L, Lou X, Yao X. [Expression and significance of Clara cell secretory protein in injury lungs of Kunming mice after n-hexane long-term inhalation]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2010;28:325-8 pubmedTo observe the expression of Clara cell secretory protein(CCSP) in the Kunming mouse model of n-hexane long-term inhalation, and to discuss the functions of Clara cell in injury lung induced by n-hexane...
- Matsumoto S, Konishi H, Maeda R, Kiryu Seo S, Kiyama H. Expression analysis of the regenerating gene (Reg) family members Reg-III? and Reg-III? in the mouse during development. J Comp Neurol. 2012;520:479-94 pubmed publisher..g., microbes) in the outer world, whereas the transient expression of Reg-III? in the nervous system may be associated with the development of the peripheral nervous system including such processes as myelination. ..
- Xu B, Chen C, Chen H, Zheng S, Bringas P, Xu M, et al. Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate fetal lung development. Development. 2011;138:925-35 pubmed publisher..This suggests a novel regulatory loop of Bmp4-Smad1-Wif1-Wnt/?-catenin in coordinating BMP and Wnt pathways to control fetal lung development. ..
- Bustos M, Mura M, Hwang D, Ludkovski O, Wong A, Keating A, et al. Depletion of bone marrow CCSP-expressing cells delays airway regeneration. Mol Ther. 2015;23:561-9 pubmed publisher..We previously reported a subpopulation of BMC that express Clara cell secretory protein (CCSP)...
- Danielian P, Bender Kim C, Caron A, Vasile E, Bronson R, Lees J. E2f4 is required for normal development of the airway epithelium. Dev Biol. 2007;305:564-76 pubmed..Importantly, the combination of no ciliated cells and excess mucous cells can account for the chronic rhinitis and increased susceptibility to opportunistic infections that causes the postnatal lethality of E2f4 mutant mice. ..
- Stripp B, Lund J, Mango G, Doyen K, Johnston C, Hultenby K, et al. Clara cell secretory protein: a determinant of PCB bioaccumulation in mammals. Am J Physiol. 1996;271:L656-64 pubmedb>Clara cell secretory protein (CCSP) is a product of nonciliated cells of the conducting airway epithelium. The normal physiological function of CCSP is unknown...
- Jaffer O, Carter A, Sanders P, Dibbern M, Winters C, Murthy S, et al. Mitochondrial-targeted antioxidant therapy decreases transforming growth factor-?-mediated collagen production in a murine asthma model. Am J Respir Cell Mol Biol. 2015;52:106-15 pubmed publisher..Mitochondrial-targeted antioxidants may be a novel approach for future asthma therapies. ..
- Yu H, He K, Li L, Sun L, Tang F, Li R, et al. Deletion of STK40 protein in mice causes respiratory failure and death at birth. J Biol Chem. 2013;288:5342-52 pubmed publisher..STK40 may associate with RCN2 to activate ERK/MAPK signaling and control the expression of multiple key regulators of lung development. ..
- Xing Y, Li A, Borok Z, Li C, Minoo P. NOTCH1 is required for regeneration of Clara cells during repair of airway injury. Stem Cells. 2012;30:946-55 pubmed publisher..The signaling pathway by which Notch1 regulates the repair process includes stimulation of Hes5 and Pax6 gene expression...
- 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..1-cre) lungs exhibit increased progenitor cell pools 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 ..
- Schuhmacher A, Guerra C, Sauzeau V, Canamero M, Bustelo X, Barbacid M. A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition. J Clin Invest. 2008;118:2169-79 pubmed publisher..In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies. ..
- Colpitts T, Billing Medel P, Friedman P, Granados E, Hayden M, Hodges S, et al. Mammaglobin is found in breast tissue as a complex with BU101. Biochemistry. 2001;40:11048-59 pubmed..We report here that mammaglobin, in breast tissue, is found as a complex with BU101. The complex was isolated from breast cancer tissue and was characterized as the biologically relevant form of mammaglobin. ..