Anti-fibrotic effects of a novel small compound on the regulation of cytokine production in a mouse model of colorectal fibrosis.
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| Abstract |
Intestinal fibrotic stricture is a major complication of inflammatory bowel disease. Despite its clinical importance, anti-fibrotic therapy has not been implemented. Transforming growth factor-β (TGF-β) is considered to be a major factor contributing to tissue fibrosis. We have previously shown that the administration of a small compound, HSc025, which promotes the nuclear translocation of YB-1 as a downstream effector of IFN-γ and antagonizes TGF-β/Smad signaling, improves fibrosis in several murine tissues. In this study, we evaluated the anti-fibrotic effect of HSc025 on colorectal fibrosis in TNBS-induced murine chronic colitis. Daily oral administration of HSc025 (3, 15 and 75 mg/kg) suppressed collagen production and decreased the severity of colorectal fibrosis in a dose-dependent manner. In addition, the local production of TGF-β was decreased after HSc025 treatment, whereas that of IL-13 and TNF-α was not affected. HSc025 administration maintained the level of IFN-γ production, even at a late stage when IFN-γ production was lost without the drug treatment. These results demonstrate that HSc025 could be a therapeutic candidate for intestinal fibrosis in inflammatory bowel disease that acts by altering the local production of cytokines, as well as by directly suppressing collagen production.
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| Authors | Jin Imai, Katsuto Hozumi, Hideaki Sumiyoshi, Masaki Yazawa, Ken-ichi Hirano, Jun Abe, Kiyoshi Higashi, Yutaka Inagaki, Tetsuya Mine |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 468 Issue 4 Pg. 554-60 (Dec 25 2015) ISSN: 1090-2104 [Electronic] United States |
| PMID | 26603932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
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