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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Main Authors: Goro Miki, Nobuko Kuroishi, Mariko Tokashiki, Sayaka Nagata, Masaji Tamura, Taku Yoshiya, Kumiko Yoshizawa-Kumagaye, Shinya Ashizuka, Joji Kato, Motoo Yamasaki, Kazuo Kitamura
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Gastrointestinal Disorders
Subjects:
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.
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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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