Journal
ONCOTARGET
Volume 6, Issue 6, Pages 4171-4179Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2878
Keywords
Radiation; Fibrosis; TGF-beta 1; ALK5; SKI2162
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Funding
- SK Chemicals Inc. Seongnam-si, Korea
- Asan Institute for Life Sciences, Seoul, Korea [2012-308]
- Nuclear Safety Research Program through Korea Radiation Safety Foundation (KORSAFe)
- Nuclear Safety and Security Commission (NSSC), Republic of Korea [1301031]
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Here we demonstrated that SKI2162, a small-molecule inhibitor of the TGF-beta type I receptor (ALK5), prevented radiation-induced fibrosis (RIF) in mice. SKI2162 inhibited phosphorylation of Smad and induction of RIF-related genes in vitro. In RIF a mouse model, SKI2162 reduced late skin reactions and leg-contracture without jeopardizing the acute skin reaction. Irradiation of mouse tissue increased COL1A2 mRNA levels, and topical administration of SKI2162 significantly inhibited this effect. Thus, these findings support that SKI2162 has potential value as novel RIF-protective agent, and could be candidate for clinical trials.
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