A new cell-permeable peptide allows successful allogeneic islet transplantation in mice

Hirofumi Noguchi; Masayuki Matsushita; Teru Okitsu; Akiyoshi Moriwaki; Kazuhito Tomizawa; Sunghyun Kang; Sheng Tian Li; Naoya Kobayashi; Shinichi Matsumoto; Koich Tanaka; Noriaki Tanaka; Hideki Matsui

doi:10.1038/nm994

A new cell-permeable peptide allows successful allogeneic islet transplantation in mice

Hirofumi Noguchi, Masayuki Matsushita, Teru Okitsu, Akiyoshi Moriwaki, Kazuhito Tomizawa, Sunghyun Kang, Sheng Tian Li, Naoya Kobayashi, Shinichi Matsumoto, Koich Tanaka, Noriaki Tanaka, Hideki Matsui

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

234 Citations (Scopus)

Abstract

Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.

Original language	English
Pages (from-to)	305-309
Number of pages	5
Journal	Nature Medicine
Volume	10
Issue number	3
DOIs	https://doi.org/10.1038/nm994
Publication status	Published - Mar 2004
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/nm994

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title = "A new cell-permeable peptide allows successful allogeneic islet transplantation in mice",

abstract = "Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.",

author = "Hirofumi Noguchi and Masayuki Matsushita and Teru Okitsu and Akiyoshi Moriwaki and Kazuhito Tomizawa and Sunghyun Kang and Li, {Sheng Tian} and Naoya Kobayashi and Shinichi Matsumoto and Koich Tanaka and Noriaki Tanaka and Hideki Matsui",

note = "Funding Information: We thank A. Rao and P. Hogan (Harvard University) for providing the GFP-NFAT-1 plasmid and other reagents; S. Bonner-Weir (Harvard University) and T. Takahashi (Tokyo University) for discussion and comments on this manuscript; and T. Ogawa and T. Shirai for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas (medical genome science) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by the Life Science Project of 21st Century, Japan, and by the Regional Research & Development Consortium Project.",

year = "2004",

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doi = "10.1038/nm994",

language = "English",

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pages = "305--309",

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T1 - A new cell-permeable peptide allows successful allogeneic islet transplantation in mice

AU - Noguchi, Hirofumi

AU - Matsushita, Masayuki

AU - Okitsu, Teru

AU - Moriwaki, Akiyoshi

AU - Tomizawa, Kazuhito

AU - Kang, Sunghyun

AU - Li, Sheng Tian

AU - Kobayashi, Naoya

AU - Matsumoto, Shinichi

AU - Tanaka, Koich

AU - Tanaka, Noriaki

AU - Matsui, Hideki

N1 - Funding Information: We thank A. Rao and P. Hogan (Harvard University) for providing the GFP-NFAT-1 plasmid and other reagents; S. Bonner-Weir (Harvard University) and T. Takahashi (Tokyo University) for discussion and comments on this manuscript; and T. Ogawa and T. Shirai for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas (medical genome science) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by the Life Science Project of 21st Century, Japan, and by the Regional Research & Development Consortium Project.

PY - 2004/3

Y1 - 2004/3

N2 - Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.

AB - Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.

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A new cell-permeable peptide allows successful allogeneic islet transplantation in mice

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