Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.
Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.
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DOI：
10.1038/ncomms5478
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发表时间：
2014-07-22
影响因子：
16.6
通讯作者：
Fukuda, M. N.
中科院分区：
文献类型：
--
作者：
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., Jr.;Nakayama, J.;Aoki, D.;Fukuda, M. N.
子宫内膜异位症是一种常见的妇科疾病，伴有盆腔疼痛和不孕。目前的治疗方法包括口服避孕药结合非甾体抗炎药或手术切除病变，所有这些都提供了暂时但不完全的治愈。在这里，我们确定了一个由细胞内化，命名为z13，使用噬菌体展示的靶向肽。由于大多数子宫内膜异位症发生在面向腹膜的器官表面，我们减去了噬菌体展示库与雌性小鼠腹膜组织和选择的噬菌体克隆结合到人子宫内膜上皮细胞。蛋白质组学分析显示z13受体是环核苷酸门控通道β3，一种分选途径蛋白。然后，我们将z13与一种胞内体逃逸肽和一种胞内体诱导肽连接起来。当这些肽共同管理到狒狒的腹膜子宫内膜异位症，病变中的细胞选择性地进行细胞凋亡，对邻近器官没有影响。因此，本研究提出了一种治疗人类腹膜子宫内膜异位症的策略。 子宫内膜异位症是一种疼痛的情况，其中子宫内膜细胞被发现在子宫外。在这里，作者鉴定了一种肽，其特异性结合子宫内膜上皮细胞上表达的受体，并使用它来诱导培养细胞和患有子宫内膜异位症的狒狒的细胞凋亡。
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. Endometriosis is a painful condition in which endometrial cells are found outside the womb. Here, the authors identify a peptide that specifically binds to a receptor expressed on endometrial epithelial cells and use it to induce apoptosis in both cultured cells and baboons with endometriosis.
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