Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.
Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.
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EDA/EDAR信号通路的药理激活在辐射引起的损伤后恢复唾液腺功能。
DOI：
10.1371/journal.pone.0112840
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Limesand KH
中科院分区：
文献类型：
--
作者：
Hill G;Headon D;Harris ZI;Huttner K;Limesand KH
头颈部癌症的放射治疗通常会导致与临床上显著的唾液减少和口干相关的邻近唾液腺的附带损伤。由于唾液腺的再生能力降低，因此通过人工唾液替代来治疗唾液过少，而不是通过腺体的功能恢复。在胚胎发育过程中，外胚层发育不良/外胚层发育不良受体（EDA/EDAR）信号通路是唾液腺发育和生长的关键因素。我们已经评估了放射诱导的唾液腺功能障碍的小鼠模型的药理学激活这一途径的影响。我们报告称，辐射后给予EDAR激动剂单克隆抗体（mAbEDAR 1）可使辐射损伤的成人唾液腺功能正常化，这是通过刺激的唾液流速确定的。此外，唾液腺结构和体内平衡恢复到照射前的水平。这些结果表明，参与唾液腺发育的途径的瞬时激活可以促进损伤后的再生和功能恢复。
Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage.
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影响因子：
5.3
作者：
Limesand, Kirsten H.;Schwertfeger, Kathryn L.;Anderson, Steven M.
通讯作者：
Anderson, Steven M.
DOI：
10.1016/j.ijrobp.2010.03.035
发表时间：
2010-10-01
影响因子：
7
作者：
Limesand, Kirsten H.;Avila, Jennifer L.;Klein, Rob R.
通讯作者：
Klein, Rob R.
DOI：
10.1002/ar.a.10045
发表时间：
2003-04-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Jaskoll, T;Zhou, YM;Melnick, M
通讯作者：
Melnick, M
DOI：
10.1073/pnas.1210662109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Baum, Bruce J.;Alevizos, Ilias;Illei, Gabor G.
通讯作者：
Illei, Gabor G.
DOI：
10.1016/j.ijrobp.2008.09.036
发表时间：
2009-02-01
影响因子：
7
作者：
Avila, Jennifer L.;Grundmann, Oliver;Burd, Randy;Limesand, Kirsten H.
通讯作者：
Limesand, Kirsten H.