Page 62 - F. Cell biology

[F. Cell biology-39]

Blockade of G-CSF reverses lung fibrosis in bleomycin

model

In-Yeong Yun¹, Jae-Hyeok Kang¹, Mi-Young Choi¹, Min-Jung Kim², Su-Jae Lee¹

¹Department of Life science, Hanyang University, Seoul 04763, Republic of Korea, ²National Radiation Emergency

Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by worsening lung function
with dyspnea and leading to the death within approximately 3 years. Because IPF-specific therapies still have not

been developed, early recognition, accurate diagnosis, and effective treatment for IPF are urgently needed. Here,

we found that G-CSF is increased in human IPF tissue and in the bleomycin induced mouse lung fibrosis model,
which induces trans-differentiation of lung epithelial cells to myofibroblasts, consequently promoting lung fibrosis
through enriching ECM components. Our results revealed that Akt signaling pathway induces expression of G-CSF

and G-CSF, acting as an autocrine factor, activates STAT3 to induce epithelial to mesenchymal transition (EMT) of
lung epithelial cells. Surprisingly, G-CSF neutralizing antibodies completely block advanced fibrosis and reverse the

fibrotic lungs to normal conditions in lung fibrosis mouse model.

Collectively, our results demonstrated that G-CSF is a major regulator of IPF through EMT of lung epithelial cells

and blockade of G-CSF may reverse the fibrosis by facilitating deactivation of myofibroblasts and suggests that G-
CSF is a potential therapeutic target to restore progressive fibrotic disorders.