Share This Article:

A Peptide Nucleic Acid to Reduce Type I Collagen Production by Fibroblast Cells

DOI: 10.4236/ojmc.2015.51001    3,374 Downloads   4,029 Views   Citations

ABSTRACT

In this study, we prepared a peptide nucleic acid (PNA) against the gene coding for the human alpha 1 chain of type I collagen. This PNA was incorporated into normal human fibroblast cells by electroporation, leading to a decrease in the mRNA level of the gene. Furthermore, mRNA for the alpha 2 chain of type I collagen was also reduced. The production of collagen protein exhibited a similar profile to the changes in mRNA. These results indicate that PNA targeting COL1A1 is effective as an antigene reagent, and opens the possibility of future clinical applications in fibroproliferative disorders.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Imamura, Y. , Tsuboi, S. , Sugiyama, T. , Kittaka, A. and Shin, Y. (2015) A Peptide Nucleic Acid to Reduce Type I Collagen Production by Fibroblast Cells. Open Journal of Medicinal Chemistry, 5, 1-8. doi: 10.4236/ojmc.2015.51001.

References

[1] Myllyharju, J. and Kivirikko, K.I. (2001) Collagens and Collagen-Related Diseases. Annals of Medicine, 33, 7-21.
http://dx.doi.org/10.3109/07853890109002055
[2] Ramirez, F., Tanaka, S. and Bou-Gharios, G. (2006) Transcriptional Regulation of the Human α2(I) Collagen Gene (COL1A2), an Informative Model System to Study Fibrotic Diseases. Matrix Biology, 25, 365-372.
http://dx.doi.org/10.1016/j.matbio.2006.05.002
[3] Eckes, B., Mauch, C., Hüppe, G. and Krieg, T. (1996) Differential Regulation of Transcription and Transcript Stability of Pro-Alpha 1(I) Collagen and Fibronectin in Activated Fibroblasts Derived from Patients with Systemic Scleroderma. The Biochemical Journal, 315, 549-554.
[4] Trojanowska, M., LeRoy, E.C., Eckes, B. and Krieg, T. (1998) Pathogenesis of Fibrosis: Type 1 Collagen and the Skin. Journal of Molecular Medicine, 76, 266-274.
http://dx.doi.org/10.1007/s001090050216
[5] Louneva, N., Saitta, B., Herrick, D.J. and Jimenez, S.A. (2003) Transcriptional Inhibition of Type I Collagen Gene Expression in Scleroderma Fibroblasts by the Antineoplastic Drug Ecteinascidin 743. The Journal of Biological Chemistry, 278, 40400-40407.
http://dx.doi.org/10.1074/jbc.M301964200
[6] Rosenbloom, J., Mendoza, F.A. and Jimenez, S.A. (2013) Strategies for Anti-Fibrotic Therapies. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1832, 1088-1103.
http://dx.doi.org/10.1016/j.bbadis.2012.12.007
[7] Massagué, J., Seoane, J. and Wotton, D. (2005) Smad Transcription Factors. Genes & Development, 19, 2783-2810.
http://dx.doi.org/10.1101/gad.1350705
[8] Challa, A.A. and Stefanovic, B. (2011) A Novel Role of Vimentin Filaments: Binding and Stabilization of Collagen mRNAs. Molecular and Cellular Biology, 31, 3773-3789.
http://dx.doi.org/10.1128/MCB.05263-11
[9] Hyrup, B. and Nielsen, P.E. (1996) Peptide Nucleic Acids (PNA): Synthesis, Properties and Potential Applications. Bioorganic & Medicinal Chemistry, 4, 5-23.
http://dx.doi.org/10.1016/0968-0896(95)00171-9
[10] Egholm, M., Buchardt, O., Christensen, L., Behrens, C., Freier, S.M., Driver, D.A., et al. (1993) PNA Hybridizes to Complementary Oligonucleotides Obeying the Watson-Crick Hydrogen-Bonding Rules. Nature, 365, 566-568.
http://dx.doi.org/10.1038/365566a0
[11] Janowski, B.A., Kaihatsu, K., Huffman, K.E., Schwartz, J.C., Ram, R., Hardy, D., et al. (2005) Inhibiting Transcription of Chromosomal DNA with Antigene Peptide Nucleic Acids. Nature Chemical Biology, 1, 210-215.
http://dx.doi.org/10.1038/nchembio724
[12] Fire, A., Xu, S.Q., Montgomery, M.K., Kostas, S.A., Driver, S.E. and Mello, C.C. (1998) Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis elegans. Nature, 391, 806-811.
http://dx.doi.org/10.1038/35888
[13] Hammond, S. M. (2005) Dicing and Slicing. FEBS Letters, 579, 5822-5829.
http://dx.doi.org/10.1016/j.febslet.2005.08.079
[14] Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989) Molecular Cloning. 2nd Edition, Cold Spring Harbor Laboratory Press, New York.
[15] Cutrona, G., Carpaneto, E.M., Ponzanelli, A., Ulivi, M., Millo, E., Scarfì, S., et al. (2003) Inhibition of the Translocated C-Myc in Burkitt’s Lymphoma by a PNA Complementary to the E mu Enhancer. Cancer Research, 63, 6144-6148.
[16] Macadangdang, B., Zhang, N., Lund, P.E., Marple, A.H., Okabe, M., Gottesman, M.M. et al. (2011) Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells. PLoS ONE, 6, e17981.
http://dx.doi.org/10.1371/journal.pone.0017981

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.