SKI2162, an inhibitor of the TGF-β type I receptor (ALK5), inhibits radiation-induced fibrosis in mice
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Jin-hong Park1, Seung-Hee Ryu1, Eun Kyung Choi1, Seung Do Ahn1, Euisun Park3, Kyung-Chul Choi2,*, Sang-wook Lee1,*
1Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
2Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea
3Life Science Research Center, SK Chemicals, Seongnam-si, Korea
*These authors have contributed equally to this work
Sang-wook Lee, e-mail: [email protected]
Kyung-Chul Choi, e-mail: [email protected]
Keywords: Radiation, Fibrosis, TGF-β1, ALK5, SKI2162
Received: September 17, 2014 Accepted: December 08, 2014 Published: February 17, 2015
Here we demonstrated that SKI2162, a small-molecule inhibitor of the TGF-β 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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