Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis

K. Sugihara, Y. Kobayashi, A. Suzuki, N. Tamura, K. Motamedchaboki, C. T. Huang, T. O. Akama, J. Pecotte, P. Frost, C. Bauer, J. B. Jimenez, J. Nakayama, Daisuke Aoki, M. N. Fukuda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.

Original languageEnglish
Article number4478
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014 Jul 22

Fingerprint

peritoneum
Endometriosis
Bacteriophages
peptides
therapy
Peritoneum
Peptides
apoptosis
organs
lesions
baboons
Cyclic Nucleotide-Gated Cation Channels
Display devices
Apoptosis
Contraceptives, Oral, Combined
pain
nucleotides
Therapeutics
classifying
cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Sugihara, K., Kobayashi, Y., Suzuki, A., Tamura, N., Motamedchaboki, K., Huang, C. T., ... Fukuda, M. N. (2014). Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. Nature Communications, 5, [4478]. https://doi.org/10.1038/ncomms5478

Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. / Sugihara, K.; Kobayashi, Y.; Suzuki, A.; Tamura, N.; Motamedchaboki, K.; Huang, C. T.; Akama, T. O.; Pecotte, J.; Frost, P.; Bauer, C.; Jimenez, J. B.; Nakayama, J.; Aoki, Daisuke; Fukuda, M. N.

In: Nature Communications, Vol. 5, 4478, 22.07.2014.

Research output: Contribution to journalArticle

Sugihara, K, Kobayashi, Y, Suzuki, A, Tamura, N, Motamedchaboki, K, Huang, CT, Akama, TO, Pecotte, J, Frost, P, Bauer, C, Jimenez, JB, Nakayama, J, Aoki, D & Fukuda, MN 2014, 'Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis', Nature Communications, vol. 5, 4478. https://doi.org/10.1038/ncomms5478
Sugihara K, Kobayashi Y, Suzuki A, Tamura N, Motamedchaboki K, Huang CT et al. Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. Nature Communications. 2014 Jul 22;5. 4478. https://doi.org/10.1038/ncomms5478
Sugihara, K. ; Kobayashi, Y. ; Suzuki, A. ; Tamura, N. ; Motamedchaboki, K. ; Huang, C. T. ; Akama, T. O. ; Pecotte, J. ; Frost, P. ; Bauer, C. ; Jimenez, J. B. ; Nakayama, J. ; Aoki, Daisuke ; Fukuda, M. N. / Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. In: Nature Communications. 2014 ; Vol. 5.
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