Home LiteratureArticle Details
PMID: 21708928 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

FoxM1 mediates the progenitor function of type II epithelial cells in repairing alveolar injury induced by Pseudomonas aeruginosa.

The Journal of experimental medicine ·Vol. 208 ·No. 7 ·2011-07-04 ·Pages 1473-84

Liu Y, Sadikot RT, Adami GR, Kalinichenko VV, Pendyala S, Natarajan V, Zhao YY, Malik AB

Abstract

The alveolar epithelium is composed of the flat type I cells comprising 95% of the gas-exchange surface area and cuboidal type II cells comprising the rest. Type II cells are described as facultative progenitor cells based on their ability to proliferate and trans-differentiate into type I cells. In this study, we observed that pneumonia induced by intratracheal instillation of Pseudomonas aeruginosa (PA) in mice increased the expression of the forkhead transcription factor FoxM1 in type II cells coincidentally with the induction of alveolar epithelial barrier repair. FoxM1 was preferentially expressed in the Sca-1(+) subpopulation of progenitor type II cells. In mice lacking FoxM1 specifically in type II cells, type II cells showed decreased proliferation and impaired trans-differentiation into type I cells. Lungs of these mice also displayed defective alveolar barrier repair after injury. Expression of FoxM1 in the knockout mouse lungs partially rescued the defective trans-differentiation phenotype. Thus, expression of FoxM1 in type II cells is essential for their proliferation and transition into type I cells and for restoring alveolar barrier homeostasis after PA-induced lung injury.

MeSH Terms
Adult Stem Cells/pathology,physiology Animals Antigens, Ly/metabolism Cell Proliferation Cell Transdifferentiation Forkhead Box Protein M1 Forkhead Transcription Factors/deficiency,genetics,physiology Gene Knockout Techniques Membrane Proteins/metabolism Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Pneumonia, Bacterial/pathology,physiopathology Pseudomonas Infections/pathology,physiopathology Pseudomonas aeruginosa/pathogenicity Pulmonary Alveoli/injuries,pathology,physiopathology Respiratory Mucosa/injuries,pathology,physiopathology
Chemicals
Antigens, Ly Forkhead Box Protein M1 Forkhead Transcription Factors Foxm1 protein, mouse Ly6a protein, mouse Membrane Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Liu Yuru
Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. yuruliu@uic.edu
Sadikot Ruxana T
Adami Guy R
Kalinichenko Vladimir V
Pendyala Srikanth
Natarajan Viswanathan
Zhao You-yang
Malik Asrar B
References (48)
48 references, click to expand
  1. Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cells.
    Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L658-67 PMID: 12922980
  2. Isolation and culture of alveolar type II cells.
    Am J Physiol. 1990 Apr;258(4 Pt 1):L134-47 PMID: 2185652
  3. Identification of bronchioalveolar stem cells in normal lung and lung cancer.
    Cell. 2005 Jun 17;121(6):823-35 PMID: 15960971
  4. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
    Cell. 2004 Sep 3;118(5):635-48 PMID: 15339667
  5. Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice.
    Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11375-80 PMID: 12177436
  6. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
    Nature. 2004 May 6;429(6987):41-6 PMID: 15129273
  7. FoxM1 regulates re-annealing of endothelial adherens junctions through transcriptional control of beta-catenin expression.
    J Exp Med. 2010 Aug 2;207(8):1675-85 PMID: 20660612
  8. The role of chemokines in neutrophil biology.
    Front Biosci. 2008 Jan 01;13:2400-7 PMID: 17981721
  9. Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa.
    J Immunol. 2006 Apr 15;176(8):4923-30 PMID: 16585588
  10. Concise review: stem cell antigen-1: expression, function, and enigma.
    Stem Cells. 2007 Jun;25(6):1339-47 PMID: 17379763
  11. The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium.
    Cell Stem Cell. 2009 Jun 5;4(6):525-34 PMID: 19497281
  12. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  13. Microscopic characterization of rabbit lung damage produced by Pseudomonas aeruginosa proteases.
    Infect Immun. 1979 Jan;23(1):150-9 PMID: 106001
  14. Renewal of alveolar epithelium in the rat following exposure to NO2.
    Am J Pathol. 1973 Feb;70(2):175-98 PMID: 4566990
  15. The lung collectins, SP-A and SP-D, modulate pulmonary innate immunity.
    Mol Immunol. 2005 Feb;42(3):279-87 PMID: 15589315
  16. Biology of alveolar type II cells.
    Respirology. 2006 Jan;11 Suppl:S12-5 PMID: 16423262
  17. Isolation of highly pure alveolar epithelial type I and type II cells from rat lungs.
    Lab Invest. 2004 Jun;84(6):727-35 PMID: 15077123
  18. Wnt signaling in lung organogenesis.
    Organogenesis. 2008 Apr;4(2):100-8 PMID: 19279721
  19. The acute respiratory distress syndrome.
    N Engl J Med. 2000 May 4;342(18):1334-49 PMID: 10793167
  20. Hierarchical organization of lung progenitor cells: is there an adult lung tissue stem cell?
    Proc Am Thorac Soc. 2008 Aug 15;5(6):695-8 PMID: 18684719
  21. Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice.
    Genes Dev. 2008 Sep 1;22(17):2308-41 PMID: 18765787
  22. Early restriction of peripheral and proximal cell lineages during formation of the lung.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10482-7 PMID: 12145322
  23. Maintenance of the mouse type II cell phenotype in vitro.
    Am J Physiol Lung Cell Mol Physiol. 2002 Aug;283(2):L256-64 PMID: 12114186
  24. Lung fluid transport in aquaporin-5 knockout mice.
    J Clin Invest. 2000 Jan;105(1):93-100 PMID: 10619865
  25. Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B expression.
    J Biol Chem. 2002 Nov 15;277(46):44310-6 PMID: 12221098
  26. Expanding the frontiers of lung biology through the creative use of alveolar epithelial cells in culture.
    Am J Physiol. 1996 Apr;270(4 Pt 1):L484-6 PMID: 8928807
  27. Epithelial stem cells of the lung: privileged few or opportunities for many?
    Development. 2006 Jul;133(13):2455-65 PMID: 16735479
  28. Differential gene expression in the distal tip endoderm of the embryonic mouse lung.
    Gene Expr Patterns. 2002 Dec;2(3-4):229-33 PMID: 12617806
  29. Role for ETS domain transcription factors Pea3/Erm in mouse lung development.
    Dev Biol. 2003 Sep 1;261(1):10-24 PMID: 12941618
  30. Commentary: Sca-1 and Cells of the Lung: A matter of Different Sorts.
    Stem Cells. 2009 Mar;27(3):606-11 PMID: 19259938
  31. Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury.
    J Clin Invest. 2006 Sep;116(9):2333-43 PMID: 16955137
  32. Misexpression of ELF5 disrupts lung branching and inhibits epithelial differentiation.
    Dev Biol. 2008 Aug 1;320(1):149-60 PMID: 18544451
  33. The forkhead box m1 transcription factor is essential for embryonic development of pulmonary vasculature.
    J Biol Chem. 2005 Jun 10;280(23):22278-86 PMID: 15817462
  34. Tracking down the stem cells of the intestine: strategies to identify adult stem cells.
    Gastroenterology. 2007 Dec;133(6):1755-60 PMID: 18054544
  35. Signaling networks in hepatic oval cell activation.
    Stem Cell Res. 2007 Nov;1(2):90-102 PMID: 19383389
  36. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis.
    Am J Pathol. 2005 May;166(5):1321-32 PMID: 15855634
  37. FOXM1c transactivates the human c-myc promoter directly via the two TATA boxes P1 and P2.
    FEBS J. 2006 Oct;273(20):4645-67 PMID: 16965535
  38. The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells.
    Development. 2009 Nov;136(22):3741-5 PMID: 19855016
  39. New and unexpected: forkhead meets ARF.
    Curr Opin Genet Dev. 2005 Feb;15(1):42-8 PMID: 15661532
  40. Pulmonary surfactant secretion in briefly cultured mouse type II cells.
    Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L331-6 PMID: 14565945
  41. Alveolar epithelial cells: differentiation and lung injury.
    Respirology. 2006 Jan;11 Suppl:S28-31 PMID: 16423267
  42. Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2.
    Exp Mol Pathol. 1975 Feb;22(1):142-50 PMID: 163758
  43. A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration.
    Nat Genet. 2008 Jul;40(7):862-70 PMID: 18536717
  44. Forkhead Box m1 transcription factor is required for perinatal lung function.
    Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19330-5 PMID: 19033457
  45. Beta-catenin/T-cell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells.
    J Biol Chem. 2010 Jan 29;285(5):3157-67 PMID: 19933277
  46. Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
    Am J Physiol Lung Cell Mol Physiol. 2005 Dec;289(6):L971-9 PMID: 16040629
  47. Transcriptional elements from the human SP-C gene direct expression in the primordial respiratory epithelium of transgenic mice.
    Dev Biol. 1993 Apr;156(2):426-43 PMID: 8462742
  48. Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro.
    Am J Physiol Lung Cell Mol Physiol. 2009 Dec;297(6):L1045-55 PMID: 19717550
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20102041
Email
yuruliu@uic.edu
Published
2011-07-04
Epub
2011-00-27
Pages
1473-84
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC3135362
Subset
IM
Grants
NHLBI NIH HHS · HL07829-16 · United States
NHLBI NIH HHS · R01 HL090152 · United States
NHLBI NIH HHS · HL090152 · United States
NHLBI NIH HHS · T32 HL007829 · United States
NHLBI NIH HHS · R01 HL105947 · United States
External Links
PubMed source DOI: 10.1084/jem.20102041 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2