EW-7197 prevents ulcerative colitis-associated fibrosis and inflammation.


Journal

Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222

Informations de publication

Date de publication:
07 2019
Historique:
received: 08 10 2018
accepted: 06 11 2018
pubmed: 28 11 2018
medline: 6 5 2020
entrez: 28 11 2018
Statut: ppublish

Résumé

EW-7197 is a transforming growth factor-β type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.

Identifiants

pubmed: 30478959
doi: 10.1002/jcp.27823
doi:

Substances chimiques

Aniline Compounds 0
Anti-Inflammatory Agents 0
Antioxidants 0
Triazoles 0
vactosertib 6T4O391P5Y

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

11654-11661

Informations de copyright

© 2018 Wiley Periodicals, Inc.

Auteurs

Maryam M Binabaj (MM)

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Fereshteh Asgharzadeh (F)

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Amir Avan (A)

Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Farzad Rahmani (F)

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Atena Soleimani (A)

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Mohammad R Parizadeh (MR)

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Gordon A Ferns (GA)

Division of Medical Education, Brighton & Sussex Medical School, Brighton, UK.

Mikhail Ryzhikov (M)

Division of Pulmonary and Critical Care Medicine, School of Medicine, Washington University, Saint Louis, Missouri.

Majid Khazaei (M)

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Seyed M Hassanian (SM)

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

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Classifications MeSH