20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease

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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Bibliographic Details
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:
adrenomedullin
polyethylene glycol
inflammatory bowel disease
colitis
dextran sulfate
Online Access:https://www.mdpi.com/2624-5647/2/4/33
Description
Summary: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.
ISSN:2624-5647

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