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PMID: 16424384 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Telomerase regulation of myofibroblast differentiation.

American journal of respiratory cell and molecular biology ·Vol. 34 ·No. 5 ·2006-05-00 ·Pages 625-33

Liu T, Hu B, Chung MJ, Ullenbruch M, Jin H, Phan SH

Abstract

Telomerase activity, which has wide expression in cancerous cells, is induced in lung proliferating fibroblasts. It is preferentially expressed in fibroblasts versus myofibroblasts. It is unknown whether regulation of telomerase expression is related to the process of fibroblast differentiation into myofibroblasts. The objective of this study was to clarify such a potential link between telomerase expression and myofibroblast differentiation. Telomerase inhibitor, 3'-azido-2',3'-dideoxythymidine, or antisense oligonucleotide to the telomerase RNA component was used to inhibit the induced fibroblast telomerase activity. The results showed that inhibition of induced telomerase increased alpha-smooth muscle actin expression, an indicator of myofibroblast differentiation. In contrast, induction of telomerase by basic fibroblast growth factor inhibited alpha-smooth muscle actin expression. These findings suggest that the loss of telomerase activity is closely associated with myofibroblast differentiation and possibly functions as a trigger for myofibroblast differentiation. Conversely, expression of telomerase suppresses myofibroblast differentiation.

MeSH Terms
Actins/genetics Animals Apoptosis/drug effects Bleomycin/pharmacology Cell Differentiation Cell Proliferation/drug effects Cell Survival/drug effects Cells, Cultured DNA-Binding Proteins/antagonists & inhibitors,metabolism Fibroblasts/cytology,drug effects Lung/cytology,drug effects Muscle Cells/cytology,drug effects Oligonucleotides, Antisense/pharmacology Phenotype Promoter Regions, Genetic/drug effects RNA/antagonists & inhibitors Rats Rats, Inbred F344 Telomerase/antagonists & inhibitors,metabolism Thionucleotides/pharmacology Time Factors Zidovudine/pharmacology
Chemicals
Actins DNA-Binding Proteins Oligonucleotides, Antisense Thionucleotides smooth muscle actin, rat telomerase RNA Bleomycin Zidovudine RNA Telomerase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Liu Tianju
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Hu Biao
Chung Myoung Ja
Ullenbruch Matt
Jin Hong
Phan Sem H
References (40)
40 references, click to expand
  1. Telomerase activity, cell proliferation, and cancer.
    Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):90-2 PMID: 9419332
  2. Inhibition of cell growth and telomerase activity of breast cancer cells in vitro by 3'-azido-3'-deoxythymidine.
    Clin Cancer Res. 1998 Mar;4(3):693-6 PMID: 9533539
  3. Irreversible telomere shortening by 3'-azido-2',3'-dideoxythymidine (AZT) treatment.
    Biochem Biophys Res Commun. 1998 May 8;246(1):107-10 PMID: 9600076
  4. Expression of TERT in early premalignant lesions and a subset of cells in normal tissues.
    Nat Genet. 1998 Jun;19(2):182-6 PMID: 9620778
  5. Inhibition of human telomerase by 2'-O-methyl-RNA.
    Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11549-54 PMID: 9751703
  6. Telomerase mediates vascular endothelial growth factor-dependent responsiveness in a rat model of hind limb ischemia.
    J Biol Chem. 2005 Apr 15;280(15):14790-8 PMID: 15687494
  7. Studies of the molecular mechanisms in the regulation of telomerase activity.
    FASEB J. 1999 Dec;13(15):2091-104 PMID: 10593857
  8. Activation of telomerase by silica in rat lung.
    Toxicol Lett. 2000 Jan 5;111(3):263-70 PMID: 10643871
  9. Inhibition of human telomerase activity by antisense phosphorothioate oligonucleotides encapsulated with the transfection reagent, FuGENE6, in HeLa cells.
    Antisense Nucleic Acid Drug Dev. 2000 Apr;10(2):87-96 PMID: 10805159
  10. Basic FGF-induced activation of telomerase in rheumatoid synoviocytes.
    Rheumatol Int. 2000;19(4):123-8 PMID: 10836521
  11. Transient expression of human telomerase extends the life span of normal human fibroblasts.
    Biochem Biophys Res Commun. 2000 Jul 14;273(3):1095-8 PMID: 10891377
  12. Induction of telomerase activity in fibroblasts from bleomycin-injured lungs.
    Am J Respir Cell Mol Biol. 2000 Oct;23(4):460-5 PMID: 11017910
  13. Complex regulatory mechanisms of telomerase activity in normal and cancer cells: how can we apply them for cancer therapy?
    Oncogene. 2002 Jan 21;21(4):688-97 PMID: 11850797
  14. Regulation of telomerase activity in rat lung fibroblasts.
    Am J Respir Cell Mol Biol. 2002 May;26(5):534-40 PMID: 11970904
  15. Transient increase in telomerase activity of proliferating fibroblasts and endothelial cells in granulation tissue of the human skin.
    Wound Repair Regen. 2002 Jan-Feb;10(1):59-66 PMID: 11983007
  16. 2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells.
    Cancer Gene Ther. 2002 Jul;9(7):624-30 PMID: 12082463
  17. Human telomerase and its regulation.
    Microbiol Mol Biol Rev. 2002 Sep;66(3):407-25, table of contents PMID: 12208997
  18. The myofibroblast in pulmonary fibrosis.
    Chest. 2002 Dec;122(6 Suppl):286S-289S PMID: 12475801
  19. Simultaneous targeting of telomeres and telomerase as a cancer therapeutic approach.
    Cancer Res. 2003 Feb 1;63(3):579-85 PMID: 12566299
  20. Fibroblast growth factor-2, but not vascular endothelial growth factor, upregulates telomerase activity in human endothelial cells.
    Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):748-54 PMID: 12676798
  21. Constitutive overexpression of human telomerase reverse transcriptase but not c-myc blocks terminal differentiation in human HaCaT skin keratinocytes.
    J Invest Dermatol. 2003 Jul;121(1):110-9 PMID: 12839571
  22. Smad3 mediates transforming growth factor-beta-induced alpha-smooth muscle actin expression.
    Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):397-404 PMID: 12702545
  23. Telomerase inhibition by retinoids precedes cytodifferentiation of leukemia cells and may contribute to terminal differentiation.
    Mol Cancer Ther. 2004 Aug;3(8):1003-9 PMID: 15299083
  24. A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiation.
    Mech Dev. 2004 Dec;121(12):1509-22 PMID: 15511642
  25. Rat lung fibroblast collagen metabolism in bleomycin-induced pulmonary fibrosis.
    J Clin Invest. 1985 Jul;76(1):241-7 PMID: 2410457
  26. Oligodeoxynucleotide stability in subcellular extracts and culture media.
    J Biochem Biophys Methods. 1986 Sep;13(2):97-102 PMID: 3772027
  27. Modified deoxyoligonucleotides stable to exonuclease degradation in serum.
    Nucleic Acids Res. 1991 Feb 25;19(4):747-50 PMID: 1850122
  28. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
    EMBO J. 1992 May;11(5):1921-9 PMID: 1582420
  29. Inhibition of human immunodeficiency virus type 1 integrase by 3'-azido-3'-deoxythymidylate.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5771-5 PMID: 8016063
  30. The RNA component of human telomerase.
    Science. 1995 Sep 1;269(5228):1236-41 PMID: 7544491
  31. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells.
    J Immunol. 1995 Oct 15;155(8):3711-5 PMID: 7561072
  32. Human naive and memory T lymphocytes differ in telomeric length and replicative potential.
    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11091-4 PMID: 7479943
  33. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines.
    Mol Cell Biol. 1996 Jan;16(1):53-65 PMID: 8524329
  34. Differentiation of immortal cells inhibits telomerase activity.
    Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12343-6 PMID: 8618897
  35. Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in bleomycin-induced pulmonary fibrosis.
    Am J Pathol. 1996 Feb;148(2):527-37 PMID: 8579115
  36. Telomere reduction and telomerase inactivation during neuronal cell differentiation.
    Biochem Biophys Res Commun. 1996 Jul 16;224(2):487-92 PMID: 8702416
  37. Telomerase activity in normal human epithelial cells.
    Oncogene. 1996 Jul 18;13(2):433-9 PMID: 8710384
  38. Down-regulation of telomerase activity is an early event in the differentiation of HL60 cells.
    Biochem Biophys Res Commun. 1996 Sep 13;226(2):329-34 PMID: 8806635
  39. Regulation of lung fibroblast alpha-smooth muscle actin expression, contractile phenotype, and apoptosis by IL-1beta.
    J Immunol. 1997 Feb 1;158(3):1392-9 PMID: 9013984
  40. Telomerase activity in human endometrium.
    Cancer Res. 1997 Feb 15;57(4):610-4 PMID: 9044835
Article Info
Journal
American journal of respiratory cell and molecular biology
Abbr.
Am J Respir Cell Mol Biol
ISSN
1044-1549
DOI
10.1165/rcmb.2005-0252OC
Published
2006-05-00
Epub
2006-00-19
Pages
625-33
Language
English
Region
United States
NLM ID
8917225
PMCID
PMC2644224
Subset
IM
Grants
NHLBI NIH HHS · HL31963 · United States
NHLBI NIH HHS · HL52285 · United States
NHLBI NIH HHS · HL77297 · United States
Corrections
CommentIn
PMID: 16618786
External Links
PubMed source DOI: 10.1165/rcmb.2005-0252OC PMC Full Text View journal details
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