| Institution: | 1. Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;2. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;3. 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;4. Division of Medical Education, Brighton & Sussex Medical School, Brighton, UK;5. Division of Pulmonary and Critical Care Medicine, School of Medicine, Washington University, Saint Louis, Missouri;6. Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran |
| Abstract: | 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. |
