Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction.
Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction.
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DOI：
10.18632/oncotarget.14583
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发表时间：
2017-02-21
期刊：
影响因子：
--
通讯作者：
Lim JY
中科院分区：
文献类型：
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作者：
Choi JS;Shin HS;An HY;Kim YM;Lim JY
辐射可引起唾液腺功能减退，在日常生活中产生不适、健康风险和功能减退。尽管对放射防护的转化研究兴趣日益浓厚，但目前还没有令人满意的治疗方法。角质细胞生长因子-1刺激唾液上皮细胞或唾液干/祖细胞的增殖。然而，其抗辐射性唾液功能减退的确切机制尚不完全清楚。我们的研究结果表明，角化细胞生长因子-1的辐射保护作用涉及减轻人腮腺上皮细胞的生长抑制和抗凋亡细胞死亡。此外，角质细胞生长因子-1通过磷酸化肌肽3-激酶-蛋白激酶B （Akt）通路保护人腮腺上皮细胞，并通过激活小鼠双分钟2抑制p53介导的凋亡。角化细胞生长因子-1局部递送至受辐射唾液腺可在体内保护辐射诱导的唾液腺细胞损伤，抑制p53介导的细胞凋亡，防止唾液腺功能减退。这表明角化细胞生长因子-1在预防辐射诱导的唾液功能减退和促进角化细胞生长因子-1局部递送系统的合理发展方面具有很好的前景。
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.