20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease
Human adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1–15) and AM (15–52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in...
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MDPI AG
2020-10-01
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Series: | Gastrointestinal Disorders |
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Online Access: | https://www.mdpi.com/2624-5647/2/4/33 |
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author | Goro Miki Nobuko Kuroishi Mariko Tokashiki Sayaka Nagata Masaji Tamura Taku Yoshiya Kumiko Yoshizawa-Kumagaye Shinya Ashizuka Joji Kato Motoo Yamasaki Kazuo Kitamura |
author_facet | Goro Miki Nobuko Kuroishi Mariko Tokashiki Sayaka Nagata Masaji Tamura Taku Yoshiya Kumiko Yoshizawa-Kumagaye Shinya Ashizuka Joji Kato Motoo Yamasaki Kazuo Kitamura |
author_sort | Goro Miki |
collection | DOAJ |
description | Human adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1–15) and AM (15–52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in HEK-293 cells stably expressing the type 1 AM receptor in a dose-dependent manner. The half-life of 20kPEG-AM was 7.4 h following subcutaneous administration in mice. We assessed the anti-colitis effect of subcutaneous 20kPEG-AM administration in the dextran sodium sulfate murine colitis model. Single and double subcutaneous injection of 20kPEG-AM significantly reduced total inflammation scores. These results suggest that 20kPEG-AM is a promising therapeutic candidate for the treatment of human inflammatory bowel diseases. |
first_indexed | 2024-03-10T15:48:03Z |
format | Article |
id | doaj.art-ac77b156f55c4ae7ad234f929d46d344 |
institution | Directory Open Access Journal |
issn | 2624-5647 |
language | English |
last_indexed | 2024-03-10T15:48:03Z |
publishDate | 2020-10-01 |
publisher | MDPI AG |
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series | Gastrointestinal Disorders |
spelling | doaj.art-ac77b156f55c4ae7ad234f929d46d3442023-11-20T16:19:17ZengMDPI AGGastrointestinal Disorders2624-56472020-10-012436637710.3390/gidisord204003320 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel DiseaseGoro Miki0Nobuko Kuroishi1Mariko Tokashiki2Sayaka Nagata3Masaji Tamura4Taku Yoshiya5Kumiko Yoshizawa-Kumagaye6Shinya Ashizuka7Joji Kato8Motoo Yamasaki9Kazuo Kitamura10Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanDivision of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanDivision of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanDivision of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanPeptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki-shi, Osaka 567-0085, JapanPeptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki-shi, Osaka 567-0085, JapanPeptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki-shi, Osaka 567-0085, JapanDivision of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanFrontier Science Research Center, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanDivision of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanDivision of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200, Kibana, Kiyotakecho, Miyazaki 889-1692, JapanHuman adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1–15) and AM (15–52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in HEK-293 cells stably expressing the type 1 AM receptor in a dose-dependent manner. The half-life of 20kPEG-AM was 7.4 h following subcutaneous administration in mice. We assessed the anti-colitis effect of subcutaneous 20kPEG-AM administration in the dextran sodium sulfate murine colitis model. Single and double subcutaneous injection of 20kPEG-AM significantly reduced total inflammation scores. These results suggest that 20kPEG-AM is a promising therapeutic candidate for the treatment of human inflammatory bowel diseases.https://www.mdpi.com/2624-5647/2/4/33adrenomedullinpolyethylene glycolinflammatory bowel diseasecolitisdextran sulfate |
spellingShingle | Goro Miki Nobuko Kuroishi Mariko Tokashiki Sayaka Nagata Masaji Tamura Taku Yoshiya Kumiko Yoshizawa-Kumagaye Shinya Ashizuka Joji Kato Motoo Yamasaki Kazuo Kitamura 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease Gastrointestinal Disorders adrenomedullin polyethylene glycol inflammatory bowel disease colitis dextran sulfate |
title | 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease |
title_full | 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease |
title_fullStr | 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease |
title_full_unstemmed | 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease |
title_short | 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease |
title_sort | 20 kda pegylated adrenomedullin as a new therapeutic candidate for inflammatory bowel disease |
topic | adrenomedullin polyethylene glycol inflammatory bowel disease colitis dextran sulfate |
url | https://www.mdpi.com/2624-5647/2/4/33 |
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