Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

Insights into the signal transduction pathways of mouse lung type II cells revealed by transcription factor profiling in the transcriptome

  • Ramana, Chilakamarti V. (Department of Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School)
  • Received : 2018.12.14
  • Accepted : 2019.03.07
  • Published : 2019.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, $NF-{\kappa}B$, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

Keywords

References

  1. Hippenstiel S, Opitz B, Schmeck B, Suttorp N. Lung epithelium as a sentinel and effector system in pneumonia: molecular mechanisms of pathogen recognition and signal transduction. Respir Res 2006;7:97. https://doi.org/10.1186/1465-9921-7-97
  2. Castell JV, Donato MT, Gomez-Lechon MJ. Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach. Exp Toxicol Pathol 2005;57 Suppl 1:189-204. https://doi.org/10.1016/j.etp.2005.05.008
  3. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997;349:1436-1442. https://doi.org/10.1016/S0140-6736(96)07495-8
  4. Maeda Y, Dave V, Whitsett JA. Transcriptional control of lungmorphogenesis. Physiol Rev 2007;87:219-244. https://doi.org/10.1152/physrev.00028.2006
  5. Perl AK, Wert SE, Loudy DE, Shan Z, Blair PA, Whitsett JA. Conditional recombination reveals distinct subsets of epithelial cells in trachea, bronchi, and alveoli. Am J Respir Cell Mol Biol 2005;33:455-462. https://doi.org/10.1165/rcmb.2005-0180OC
  6. Fehrenbach H. Alveolar epithelial type II cell: defender of the alveolus revisited. Respir Res 2001;2:33-46. https://doi.org/10.1186/rr36
  7. Corti M, Brody AR, Harrison JH. Isolation and primary culture of murine alveolar type II cells. Am J Respir Cell Mol Biol 1996;14:309-315. https://doi.org/10.1165/ajrcmb.14.4.8600933
  8. Michael P, Brabant D, Bleiblo F, Ramana CV, Rutherford M, Khurana S, et al. Influenza A induced cellular signal transduction pathways. J Thorac Dis 2013;5 Suppl 2:S132-141.
  9. Xu L, Yoon H, Zhao MQ, Liu J, Ramana CV, Enelow RI. Cutting edge: pulmonary immunopathology mediated by antigen-specific expression of TNF-alpha by antiviral CD8+ T-cells. J Immunol 2004;173:721-725. https://doi.org/10.4049/jimmunol.173.2.721
  10. Wright JR, Dobbs LG. Regulation of pulmonary surfactant secretion and clearance. Annu Rev Physiol 1991;53:395-414. https://doi.org/10.1146/annurev.ph.53.030191.002143
  11. Morales Johansson H, Newman DR, Sannes PL. Whole-genome analysis of temporal gene expression during early transdifferentiation of human lung alveolar epithelial type 2 cells in vitro. PLoS One 2014;9:e93413. https://doi.org/10.1371/journal.pone.0093413
  12. Newman V, Gonzalez RF, Matthay MA, Dobbs LG. A novel alveolar type I cell-specific biochemical marker of human acute lung injury. Am J Respir Crit Care Med 2000;161:990-995. https://doi.org/10.1164/ajrccm.161.3.9901042
  13. Boylan GM, Pryde JG, Dobbs LG, McElroy MC. Identification of a novel antigen on the apical surface of rat alveolar epithelial type II and Clara cells. Am J Physiol Lung Cell Mol Physiol 2001;280:L1318-L1326. https://doi.org/10.1152/ajplung.2001.280.6.L1318
  14. Roper JM, Staversky RJ, Finkelstein JN, Keng PC, O'Reilly MA. Identification and isolation of mouse type II cells on the basis of intrinsic expression of enhanced green fluorescent protein. Am J Physiol Lung Cell Mol Physiol 2003;285:L691-700. https://doi.org/10.1152/ajplung.00034.2003
  15. Shyamsundar R, Kim YH, Higgins JP, Montgomery K, Jorden M, Sethuraman A, et al. A DNA microarray survey of gene expression in normal human tissues. Genome Biol 2005;6:R22. https://doi.org/10.1186/gb-2005-6-3-r22
  16. Mariani TJ, Reed JJ, Shapiro SD. Expression profiling of the developing mouse lung: insights into the establishment of the extracellular matrix. Am J Respir Cell Mol Biol 2002;26:541-548. https://doi.org/10.1165/ajrcmb.26.5.2001-00080c
  17. Martinez JM, Afshari CA, Bushel PR, Masuda A, Takahashi T, Walker NJ. Differential toxicogenomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in malignant and nonmalignant human airway epithelial cells. Toxicol Sci 2002;69:409-423. https://doi.org/10.1093/toxsci/69.2.409
  18. Dave NB, Kaminski N. Analysis of microarray experiments for pulmonary fibrosis. Methods Mol Med 2005;117:333-358.
  19. Ballard PL, Lee JW, Fang X, Chapin C, Allen L, Segal MR, et al. Regulated gene expression in cultured type II cells of adult human lung. Am J Physiol Lung Cell Mol Physiol 2010;299:L36-L50. https://doi.org/10.1152/ajplung.00427.2009
  20. Xu Y, Ikegami M, Wang Y, Matsuzaki Y, Whitsett JA. Gene expression and biological processes influenced by deletion of Stat3 in pulmonary type II epithelial cells. BMC Genomics 2007;8:455. https://doi.org/10.1186/1471-2164-8-455
  21. Ramana CV, Chintapalli J, Xu L, Alia C, Zhou J, Bruder D, et al. Lung epithelial NF-kappaB and Stat1 signaling in response to CD8+ T-cell antigen recognition. J Interferon Cytokine Res 2006;26:318-327. https://doi.org/10.1089/jir.2006.26.318
  22. Nichane M, Javed A, Sivakamasundari V, Ganesan M, Ang LT, Kraus P, et al. Isolation and 3D expansion of multipotent Sox9(+) mouse lung progenitors. Nat Methods 2017;14:1205-1212. https://doi.org/10.1038/nmeth.4498
  23. Berhane K, Boggaram V. Identification of a novel DNA regulatory element in the rabbit surfactant protein B (SP-B) promoter that is a target for ATF/CREB and AP-1 transcription factors. Gene 2001;268:141-151. https://doi.org/10.1016/S0378-1119(01)00417-6
  24. Glasser SW, Burhans MS, Eszterhas SK, Bruno MD, Korfhagen TR. Human SP-C gene sequences that confer lung epithelium-specific expression in transgenic mice. Am J Physiol Lung Cell Mol Physiol 2000;278:L933-L945. https://doi.org/10.1152/ajplung.2000.278.5.L933
  25. Gong X, Sun Z, Cui D, Xu X, Zhu H, Wang L, et al. Isolation and characterization of lung resident mesenchymal stem cells capable of differentiating into alveolar epithelial type II cells. Cell Biol Int 2014;38:405-411. https://doi.org/10.1002/cbin.10240
  26. Lekstrom-Himes J, Xanthopoulos KG. Biological role of the CCAAT/enhancer-binding protein family of transcription factors. J Biol Chem 1998;273:28545-28548. https://doi.org/10.1074/jbc.273.44.28545
  27. Reddy NM, Potteti HR, Mariani TJ, Biswal S, Reddy SP. Conditional deletion of Nrf2 in airway epithelium exacerbates acute lung injury and impairs the resolution of inflammation. Am J Respir Cell Mol Biol 2011;45:1161-1168. https://doi.org/10.1165/rcmb.2011-0144OC
  28. Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 2003;4:P3. https://doi.org/10.1186/gb-2003-4-5-p3
  29. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 2004;101:6062-6067. https://doi.org/10.1073/pnas.0400782101
  30. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 1998;95:14863-14868. https://doi.org/10.1073/pnas.95.25.14863
  31. Rosenfeld MG, Lunyak VV, Glass CK. Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes Dev 2006;20:1405-1428. https://doi.org/10.1101/gad.1424806
  32. Inoue K, Takano H, Kaewamatawong T, Shimada A, Suzuki J, Yanagisawa R, et al. Role of metallothionein in lung inflammation induced by ozone exposure in mice. Free Radic Biol Med 2008;45:1714-1722. https://doi.org/10.1016/j.freeradbiomed.2008.09.008
  33. Kurakula K, Vos M, Logiantara A, Roelofs JJ, Nieuwenhuis MA, Koppelman GH, et al. Nuclear receptor Nur77 attenuates airway inflammation in mice by suppressing NF-kappaB activity in lung epithelial cells. J Immunol 2015;195:1388-1398. https://doi.org/10.4049/jimmunol.1401714
  34. Suzuki T, Aizawa K, Matsumura T, Nagai R. Vascular implications of the Kruppel-like family of transcription factors. Arterioscler Thromb Vasc Biol 2005;25:1135-1141. https://doi.org/10.1161/01.ATV.0000165656.65359.23
  35. Winkler GS. The mammalian anti-proliferative BTG/Tob protein family. J Cell Physiol 2010;222:66-72. https://doi.org/10.1002/jcp.21919
  36. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001;11:372-377. https://doi.org/10.1016/S0962-8924(01)02064-5
  37. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 2002;109 Suppl:S81-96. https://doi.org/10.1016/S0092-8674(02)00703-1
  38. Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis. Gene 2001;273:1-11. https://doi.org/10.1016/S0378-1119(01)00551-0
  39. Ludwig S, Pleschka S, Planz O, Wolff T. Ringing the alarm bells: signalling and apoptosis in influenza virus infected cells. Cell Microbiol 2006;8:375-386. https://doi.org/10.1111/j.1462-5822.2005.00678.x
  40. Chang Y, Edeen K, Lu X, De Leon M, Mason RJ. Keratinocyte growth factor induces lipogenesis in alveolar type II cells through a sterol regulatory element binding protein-1c-dependent pathway. Am J Respir Cell Mol Biol 2006;35:268-274. https://doi.org/10.1165/rcmb.2006-0037OC
  41. Zhang S, Che D, Yang F, Chi C, Meng H, Shen J, et al. Tumor-associated macrophages promote tumor metastasis via the TGF-beta/SOX9 axis in non-small cell lung cancer. Oncotarget 2017;8:99801-99815. https://doi.org/10.18632/oncotarget.21068
  42. Symon A, Harley V. SOX9: A genomic view of tissue specific expression and action. Int J Biochem Cell Biol 2017;87:18-22. https://doi.org/10.1016/j.biocel.2017.03.005
  43. Voronkova MA, Luanpitpong S, Rojanasakul LW, Castranova V, Dinu CZ, Riedel H, et al. SOX9 regulates cancer stem-like properties and metastatic potential of single-walled carbon nanotube-exposed cells. Sci Rep 2017;7:11653. https://doi.org/10.1038/s41598-017-12037-8
  44. Wan H, Luo F, Wert SE, Zhang L, Xu Y, Ikegami M, et al. Kruppel-like factor 5 is required for perinatal lung morphogenesis and function. Development 2008;135:2563-2572. https://doi.org/10.1242/dev.021964
  45. Quinlan T, Spivack S, Mossman BT. Regulation of antioxidant enzymes in lung after oxidant injury. Environ Health Perspect 1994;102 Suppl 2:79-87.
  46. Reddy NM, Kleeberger SR, Yamamoto M, Kensler TW, Scollick C, Biswal S, et al. Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection. Physiol Genomics 2007;32:74-81. https://doi.org/10.1152/physiolgenomics.00126.2007
  47. Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009;284:13291-13295. https://doi.org/10.1074/jbc.R900010200
  48. Reddy NM, Kleeberger SR, Cho HY, Yamamoto M, Kensler TW, Biswal S, et al. Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am J Respir Cell Mol Biol 2007;37:3-8. https://doi.org/10.1165/rcmb.2007-0004RC
  49. Anttila S, Raunio H, Hakkola J. Cytochrome P450-mediated pulmonary metabolism of carcinogens: regulation and cross-talk in lung carcinogenesis. Am J Respir Cell Mol Biol 2011;44:583-590. https://doi.org/10.1165/rcmb.2010-0189RT
  50. Takano H, Inoue K, Yanagisawa R, Sato M, Shimada A, Morita T, et al. Protective role of metallothionein in acute lung injury induced by bacterial endotoxin. Thorax 2004;59:1057-1062. https://doi.org/10.1136/thx.2004.024232
  51. Murphy EP, Crean D. Molecular interactions between NR4A orphan nuclear receptors and NF-kappaB are required for appropriate inflammatory responses and immune cell homeostasis. Biomolecules 2015;5:1302-1318. https://doi.org/10.3390/biom5031302
  52. Akella A, Deshpande SB. Pulmonary surfactants and their role in pathophysiology of lung disorders. Indian J Exp Biol 2013;51:5-22.
  53. Ware LB, Matthay MA. Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair. Am J Physiol Lung Cell Mol Physiol 2002;282:L924-L940. https://doi.org/10.1152/ajplung.00439.2001
  54. Adachi J, Kumar C, Zhang Y, Mann M. In-depth analysis of the adipocyte proteome by mass spectrometry and bioinformatics. Mol Cell Proteomics 2007;6:1257-1273. https://doi.org/10.1074/mcp.M600476-MCP200
  55. Flodby P, Barlow C, Kylefjord H, Ahrlund-Richter L, Xanthopoulos KG. Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha. J Biol Chem 1996;271:24753-24760. https://doi.org/10.1074/jbc.271.40.24753
  56. Matsuzaki Y, Besnard V, Clark JC, Xu Y, Wert SE, Ikegami M, et al. STAT3 regulates ABCA3 expression and influences lamellar body formation in alveolar type II cells. Am J Respir Cell Mol Biol 2008;38:551-558. https://doi.org/10.1165/rcmb.2007-0311OC
  57. Lee CM, Wu J, Xia Y, Hu J. ESE-1 in early development: approaches for the future. Front Cell Dev Biol 2016;4:73.
  58. Wang H, Yu Z, Huo S, Chen Z, Ou Z, Mai J, et al. Overexpression of ELF3 facilitates cell growth and metastasis through PI3K/Akt and ERK signaling pathways in non-small cell lung cancer. Int J Biochem Cell Biol 2018;94:98-106. https://doi.org/10.1016/j.biocel.2017.12.002
  59. Lizio M, Harshbarger J, Abugessaisa I, Noguchi S, Kondo A, Severin J, et al. Update of the FANTOM web resource: high resolution transcriptome of diverse cell types in mammals. Nucleic Acids Res 2017;45:D737-D743. https://doi.org/10.1093/nar/gkw995