Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress

被引:0
|
作者
Hu, Meijun [1 ]
Hu, Liang [2 ]
Yang, Tao [2 ]
Zhou, Bowen [2 ]
Feng, Xuanhe [2 ]
Fan, Zhipeng [1 ]
Shan, Zhaochen [2 ]
机构
[1] Capital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cells Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstruc, Beijing 100050, Peoples R China
[2] Capital Med Univ, Sch Stomatol, Outpatient Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R China
基金
中国国家自然科学基金;
关键词
ionizing radiation; Hedgehog pathway; salivary gland (SG) injury; oxidative stress; microvessel; NECK-CANCER-PATIENTS; SONIC HEDGEHOG; INDUCED HYPOSALIVATION; CELLULAR SENESCENCE; XEROSTOMIA; HEAD; HYPOFUNCTION; DELIVERY; THERAPY;
D O I
10.3390/antiox13080904
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).
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页数:17
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