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, D. Aoki, M. N. Fukuda

Research output: Contribution to journalArticle

10 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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis'. Together they form a unique fingerprint.

  • Cite this

    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, D., & 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