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

doi:10.1038/ncomms5478

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 journal › Article › peer-review

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 language	English
Article number	4478
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5478
Publication status	Published - 22-07-2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

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@article{11c05bb9a0994151a2474e067cb49e79,

title = "Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis",

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.",

author = "K. Sugihara and Y. Kobayashi and A. Suzuki and N. Tamura and K. Motamedchaboki and Huang, {C. T.} and Akama, {T. O.} and J. Pecotte and P. Frost and C. Bauer and Jimenez, {J. B.} and J. Nakayama and D. Aoki and Fukuda, {M. N.}",

note = "Funding Information: We thank Dr Erkki Ruoslahti of the Sanford-Burnham Medical Research Institute for providing us with a peptide display phage library and valuable suggestions; Drs Ze{\textquoteright}ev Ronai and Sara Courtneidge for their critical reading of the manuscript; Drs Edward Dick, Jahnni Robinson, Wade Hodgson, Terry Naeglin, Manuel Aguilar and Jennifer Diaz of the Texas Biomedical Research Institute for their assistance with baboon experiments; and Dr Elise Lamar for editing the manuscript. This study was supported by an NIH grant HD43108 (to M.N.F.), a Grant-in-Aid for Scientific Research B-18390113 (to J.N.), B-16390478 (to D.A.), B-00265878 (to K.S.) and CER-24659726 (to K.S.) from the Japan Society for the Promotion of Science.",

year = "2014",

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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, D.; Fukuda, M. N.

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

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis

AU - Sugihara, K.

AU - Kobayashi, Y.

AU - Suzuki, A.

AU - Tamura, N.

AU - Motamedchaboki, K.

AU - Huang, C. T.

AU - Akama, T. O.

AU - Pecotte, J.

AU - Frost, P.

AU - Bauer, C.

AU - Jimenez, J. B.

AU - Nakayama, J.

AU - Aoki, D.

AU - Fukuda, M. N.

N1 - Funding Information: We thank Dr Erkki Ruoslahti of the Sanford-Burnham Medical Research Institute for providing us with a peptide display phage library and valuable suggestions; Drs Ze’ev Ronai and Sara Courtneidge for their critical reading of the manuscript; Drs Edward Dick, Jahnni Robinson, Wade Hodgson, Terry Naeglin, Manuel Aguilar and Jennifer Diaz of the Texas Biomedical Research Institute for their assistance with baboon experiments; and Dr Elise Lamar for editing the manuscript. This study was supported by an NIH grant HD43108 (to M.N.F.), a Grant-in-Aid for Scientific Research B-18390113 (to J.N.), B-16390478 (to D.A.), B-00265878 (to K.S.) and CER-24659726 (to K.S.) from the Japan Society for the Promotion of Science.

PY - 2014/7/22

Y1 - 2014/7/22

N2 - 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.

AB - 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.

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

Abstract

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