Strategies for Overcoming Pulmonary Fibrosis

Yun-Sil Lee

Graduate School of Pharmaceutical Sciences, Ewha Womans University

We have previously developed a mouse model simulating clinical SBRT and have used the model to validate the induction of lung fibrosis by high-dose ionizing radiation (IR). The regimen was similar to that used for human therapy reflecting the understanding of the clinically related IR-mediated normal cell damage like fibrosis. To identify molecular signatures for lung fibrosis, we further examined the fibrosis process at 4 weeks from irradiated region from mouse lung tissues after IR and identified targets for lung fibrosis. Moreover, we also identified another molecular targets in lung fibrosis development. Hsp27 expression was increased during IR-induced lung fibrosis, and functional inhibition of Hsp27 using a small molecule ameliorated lung fibrosis. While investigating mechanisms of Hsp27 in the development of lung fibrosis, we found that IkBα-NFkB signaling activation by direct interaction of IkBα with Hsp27, is involved in the EMT process that is tightly connected to the development of IR-induced lung fibrosis. Moreover, we also investigated that miR-15 was involved in inhibition of Smurf2-mediated Hsp27 degradation, especially phosphorylated forms of Hsp27.