EW‐7197 prevents ulcerative colitis‐associated fibrosis and inflammation

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.

TGF‐β as a driver of fibrosis: physiological roles and therapeutic opportunities

“…Treatment with vactosertib reduces Smad2 and Smad3 activation and collagen synthesis across all four models [189]. Additionally, in two models of ulcerative colitis, vactosertib reduces fibrotic gene expression and collagen accumulation in colon tissue, although this may be secondary to reduction in mucosal damage [190,191]. Consistent with these results, SB525334, an orally adsorbed, selective TGF‐βRI kinase inhibitor, inhibits bleomycin‐induced lung fibrosis in mice, reducing Smad2 and Smad3 activation, and collagen and fibronectin expression, and improving lung histology with reduced collagen accumulation in the lung parenchyma [192,193].…”

Protective effect of Gloeostereum�incarnatum on ulcerative colitis via modulation of Nrf2/NF‑κB signaling in C57BL/6 mice

“…Furthermore, TGF-β serves a role in pro-inflammatory mediator production during the development of UC, which can regulate the levels of ILs, TNFs and IFNs ( 56 ). During the development of UC, signaling of the receptor-interacting protein kinase 3 can upregulate the expression of repair-associated cytokines, including cyclooxygenase 2 and IL-22 ( 57 ).…”

Molecular hydrogen is comparable to sulfasalazine as a treatment for DSS-induced colitis in mice

“…In the present study we induced an acute mouse model of colitis using 1 % DSS in drinking water, as has been described previously (Binabaj et al, 2019[ 3 ]). Consistent with previous data, we found that DSS led to symptoms of colitis, and that treatment with molecular hydrogen and or sulfasalazine exerted protective effects.…”