Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction

Abstract

// Jeong-Seok Choi 1, 2, * , Hyun-Soo Shin 1, 2, * , Hye-Young An 1, 2 , Young-Mo Kim 1, 2 , Jae-Yol Lim 1, 2 1 Department of Otorhinolaryngology-Head and Neck Surgery, Incheon, Republic of Korea 2 Translational Research Center, Incheon, Republic of Korea * These authors are contributed equally to this work Correspondence to: Jae-Yol Lim, email: jylim@inha.ac.kr Keywords: salivary glands, irradiation, xerostomia, KGF-1, apoptosis Received: November 02, 2016      Accepted: December 28, 2016      Published: January 10, 2017 ABSTRACT Irradiation can cause salivary gland hypofunction, with hyposalivation producing discomfort, health risks, and reducing function in daily life. Despite increasing translational research interest in radioprotection, there are no satisfactory treatments available. Keratinocyte growth factor-1 stimulates proliferation of salivary epithelial cells or salivary stem/progenitor cells. However, the exact mechanism of its radioprotection against radiation-induced salivary hypofunction is not fully elucidated. Our results reveal that the radioprotective effects of keratinocyte growth factor-1 involved alleviation of growth inhibition and anti-apoptotic cell death of human parotid epithelial cells. Furthermore, keratinocyte growth factor-1 protected human parotid epithelial cells through the phosphoinositide 3-kinase – protein kinase B (Akt) pathway and inhibition of p53-mediated apoptosis through activation of mouse double minute 2. Local delivery of keratinocyte growth factor-1 into the irradiated salivary glands could protect radiation-induced salivary cell damages, suppress p53-mediated apoptosis and prevent salivary hypofunction in vivo . This suggests that keratinocyte growth factor-1 is a promising candidate to prevent radiation-induced salivary hypofunction and raise rational development keratinocyte growth factor-1 local delivery system.